Search

Your search keyword '"Formation, élaboration de nanomatériaux et cristaux (FENNEC)"' showing total 53 results
Start Over Author "Formation, élaboration de nanomatériaux et cristaux (FENNEC)"
53 results on '"Formation, élaboration de nanomatériaux et cristaux (FENNEC)"'

1. Photoluminescent Recognition of Strong Alcoholic Beverages with Carbon Nanoparticles

Author

Thierry Clopeau, Valeriy A. Skryshevsky, Vladyslav V. Lisnyak, Vladimir Lysenko, Alexander N. Zaderko, I.I. Ivanov, Institute of High Technologies [Kyiv], Taras Shevchenko National University of Kyiv, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Department of Chemistry, Taras Shevchenko National University of Kyiv, and University of Prešov

Subjects
inorganic chemicals, Aromatic compounds, Materials science, Photoluminescence, Annealing (metallurgy), General Chemical Engineering, education, chemistry.chemical_element, Alcohol, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Article, Beverages, [SPI]Engineering Sciences [physics], chemistry.chemical_compound, [CHIM]Chemical Sciences, QD1-999, health care economics and organizations, [PHYS]Physics [physics], Ethanol, Sensors, Carbonization, technology, industry, and agriculture, General Chemistry, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Chemistry, Chemical engineering, chemistry, Alcohols, Mixtures, Anhydrous, 0210 nano-technology, Citric acid, Carbon
Abstract

International audience; A simple sensitive method for nonspecific recognition of armagnac, cognac, whiskey, and ethanol/water mixture was developed by using photoluminescence (PL) of carbon nanoparticles (NPs). The carbon NPs were synthesized from the mixture of urea and anhydrous citric acid, followed by few annealing processes to achieve the full effect by solvothermal carbonization. PL features of carbon NPs depend on the alcohol environments in which the NPs are dispersed. PL/PL excitation maps of the alcoholic beverages were mathematically treated, and a final principal component analysis diagram allows visualization of different clusters corresponding to each beverage. The optimal measurement conditions (concentration of NPs in colloidal solution and excitation wavelength) were defined to ensure a reliable recognition level.

Published
2021

2. Breaking photoswitch activation depth limit using ionising radiation stimuli adapted to clinical application

Author

Alban Guesdon-Vennerie, Patrick Couvreur, Fatoumia Ali, Frédéric Pouzoulet, Christophe Roulin, Immaculada Martínez-Rovira, Guillaume Bernadat, François-Xavier Legrand, Claudie Bourgaux, Cyril Lucien Mazars, Sergio Marco, Sylvain Trépout, Simona Mura, Sébastien Mériaux, Guillaume Bort, Institut Galien Paris-Saclay (IGPS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Curie, PSL Research University, Translational Research Department, Experimental Radiotherapy Platform, UMR 1288, F-91405, Orsay, France, Ionizing Radiation Research Group, Physics Department, Universitat Autònoma de Barcelona, 08193 Bellaterra, Cerdanyola del Vallès, Barcelona, Spain, Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), Chimie, Modélisation et Imagerie pour la Biologie [Orsay], Université Paris-Sud - Paris 11 (UP11)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Building large instruments for neuroimaging: from population imaging to ultra-high magnetic fields (BAOBAB), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), ANR-PDOC201-30008-01, and European Project: 663704,H2020,H2020-SMEINST-1-2014,ISO-COLD(2015)

Subjects
Photons, Multidisciplinary, Radiation, Ionizing, General Physics and Astronomy, [CHIM]Chemical Sciences, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract

Electromagnetic radiation-triggered therapeutic effect has attracted a great interest over the last 50 years. However, translation to clinical applications of photoactive molecular systems developed to date is dramatically limited, mainly because their activation requires excitation by low-energy photons from the ultraviolet to near infra-red range, preventing any activation deeper than few millimetres under the skin. Herein we conceive a strategy for photosensitive-system activation potentially adapted to biological tissues without any restriction in depth. High-energy stimuli, such as those employed for radiotherapy, are used to carry energy while molecular activation is provided by local energy conversion. This concept is applied to azobenzene, one of the most established photoswitches, to build a radioswitch. The radiation-responsive molecular system developed is used to trigger cytotoxic effect on cancer cells upon gamma-ray irradiation. This breakthrough activation concept is expected to expand the scope of applications of photosensitive systems and paves the way towards the development of original therapeutic approaches.

Published
2022

3. Radiosensitization Effect of AGuIX, a Gadolinium-Based Nanoparticle, in Nonsmall Cell Lung Cancer

Author

Liqing Du, Yanan Du, Olivier Tillement, Yan Wang, Qin Wang, Yang Liu, Ningning He, François Lux, Chang Xu, Hao Sun, Yi Xie, Zhenhua Lin, Qiang Liu, Jinhan Wang, Géraldine Leduc, Hong Zhang, Tristan Doussineau, Kaihua Ji, Chinese Academy of Medical Sciences and Peking Union Medical College, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), NH TherAguix SA [Meylan], and IMP - Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China

Subjects
Male, Radiation-Sensitizing Agents, Radiosensitizer, Lung Neoplasms, Materials science, DNA Repair, DNA repair, medicine.medical_treatment, Gadolinium, Metal Nanoparticles, Mice, Nude, chemistry.chemical_element, Antineoplastic Agents, Apoptosis, [SPI]Engineering Sciences [physics], 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Radiation, Ionizing, medicine, Animals, Humans, [CHIM]Chemical Sciences, DNA Breaks, Double-Stranded, General Materials Science, Lung, Radiation resistance, 030304 developmental biology, [PHYS]Physics [physics], 0303 health sciences, medicine.diagnostic_test, Cancer, Magnetic resonance imaging, medicine.disease, Xenograft Model Antitumor Assays, 3. Good health, Radiation therapy, chemistry, Cell culture, 030220 oncology & carcinogenesis, Cancer research
Abstract

International audience; Radiotherapy is the main treatment for cancer patients. A major concern in radiotherapy is the radiation resistance of some tumors, such as human nonsmall cell lung cancer. However, the radiation dose delivered to the tumors is often limited by the possibility of collateral damage to surrounding healthy tissues. A new and efficient gadolinium-based nanoparticle, AGuIX, has recently been developed for magnetic resonance imaging-guided radiotherapy and has been proven to act as an efficient radiosensitizer. The amplified radiation effects of AGuIX nanoparticles appear to be due to the emission of low-energy photoelectrons and Auger electron interactions. We demonstrated that AGuIX nanoparticles exacerbated radiation-induced DNA double-strand break damage and reduced DNA repair in the H1299 nonsmall cell lung cancer cell line. Furthermore, we observed a significant improvement in tumor cell damage and growth suppression, under radiation therapy, with the AGuIX nanoparticles in a H1299 mouse xenograft model. This study paves the way for research into the radiosensitization mechanism of AGuIX nanoparticles and provides a scientific basis for the use of AGuIX nanoparticles as radiosensitizing drugs.

Published
2020

4. Toxic and Physiological Metal Uptake and Release by Human Serum Transferrin

Author

Josiah D. Ruberry, Jack T. Fuller, Jon I. Mujika, Michael R. Nechay, Marie Victor, Anastassia N. Alexandrova, Xabier Lopez, Wei Li, David J. Reilley, Department of Chemistry and Biochemistry [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Department of Chemistry and Chemical Biology [Harvard], Harvard University [Cambridge], Kimika Fakultatea, Euskal Herriko Unibertsitatea, and Donostia International Physics Center (DIPC), and California NanoSystems Institute [Los Angeles] (CNSI)

Subjects
Biophysics, Metal Binding Site, Protonation, Molecular Dynamics Simulation, Ferric Compounds, Metal, [SPI]Engineering Sciences [physics], 03 medical and health sciences, Molecular dynamics, 0302 clinical medicine, Transition metal, Humans, [CHIM]Chemical Sciences, Cytotoxicity, 030304 developmental biology, [PHYS]Physics [physics], chemistry.chemical_classification, 0303 health sciences, Transferrin, Biological Transport, Articles, chemistry, Metals, visual_art, Drug delivery, visual_art.visual_art_medium, 030217 neurology & neurosurgery
Abstract

International audience; An atomistic understanding of metal transport in the human body is critical to anticipate the side effects of metal-based therapeutics and holds promise for new drugs and drug delivery designs. Human serum transferrin (hTF) is a central part of the transport processes because of its ubiquitous ferrying of physiological Fe(III) and other transition metals to tightly controlled parts of the body. There is an atomistic mechanism for the uptake process with Fe(III), but not for the release process, or for other metals. This study provides initial insight into these processes for a range of transition metals—Ti(IV), Co(III), Fe(III), Ga(III), Cr(III), Fe(II), Zn(II)—through fully atomistic, extensive quantum mechanical/discrete molecular dynamics sampling and provides, to our knowledge, a new technique we developed to calculate relative binding affinities between metal cations and the protein. It identifies protonation of Tyr188 as a trigger for metal release rather than protonation of Lys206 or Lys296. The study identifies the difficulty of metal release from hTF as potentially related to cytotoxicity. Simulations identify a few critical interactions that stabilize the metal binding site in a flexible, nuanced manner.

Published
2020

5. The design of a scintillation system based on SiPMs integrated with gain correction functionality

Author

Jang-Guen Park, Jinho Moon, Zhenhua Lin, Benoit Hautefeuille, Sung-Hee Jung, AXINT SAS, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and Korea Atomic Energy Research Institute [Daejeon, south Korea] (KAERI)

Subjects
020209 energy, Gain correction, 02 engineering and technology, Scintillator, 7. Clean energy, 030218 nuclear medicine & medical imaging, [SPI]Engineering Sciences [physics], 03 medical and health sciences, 0302 clinical medicine, Optics, Silicon photomultiplier, Minimum detectable gamma energy, 0202 electrical engineering, electronic engineering, information engineering, [CHIM]Chemical Sciences, Energy resolution, [PHYS]Physics [physics], Physics, Scintillation, business.industry, SiPM configuration, Resolution (electron density), Photoelectric effect, lcsh:TK9001-9401, Nuclear Energy and Engineering, lcsh:Nuclear engineering. Atomic power, business, Energy (signal processing), Voltage
Abstract

Use of SiPM has been considered as an alternative to PMT, because of its compact size, low-operating voltage, non-sensitive to electromagnetic, low costs and so on. The main limitation for the use of SiPM is due to its small sensitive area compared to PMT that limits the light collection, and therefore the sensor energy resolution. In this article we studied the effect of increasing the number of SiPM by connecting them in parallel to increase the active detection area. This allowed us to compare the different energy resolution measurements. 137Cs has been selected as reference to study the energy resolution for 662 keV gamma-rays. Another investigation was to compare the minimum detectable gamma energy under various SiPM configurations. It has been found that the use of 4 SiPM arrays can greatly improve the energy resolution up to 4% than only one SiPM array, meanwhile use of more than 2 SiPM arrays does not increase the energy resolution significantly. Thus we can conclude that for a large area of cylindrical scintillator (3 × 3 inches), the use of SiPMs are limited to a certain number or certain active area depending on the commercial SiPMs, and its cost should be less than traditional PMT for the cost-effective and compact size considerations. It is well known that the gain of SiPM varies with temperature. In this article, we also calibrated gain to guarantee the same position of photoelectric peak in response of different temperatures. Keywords: SiPM configuration, Energy resolution, Minimum detectable gamma energy

Published
2020

6. Identification de fragments moléculaires en équilibre avec des nanoparticules ultrasiloxanes de polysiloxane

Author

Paul Rocchi, Lucie Labied, Tristan Doussineau, Michel Julien, Barbara Giroud, Emmanuelle Vulliet, Jérôme Randon, Olivier Tillement, Agnès Hagège, François Lux, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Separative Methods - Techniques séparatives (TechSep), Institut des Sciences Analytiques (ISA), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), NHTheraguix [Crolles], Centre d'études spatiales de la biosphère (CESBIO), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), TRACES - Technologie et Recherche en Analyse Chimique pour l'Environnement et la Santé, and ANR-18-CE17-0025,ANALYTAGUIX,Caractérisation analytique de nanoparticules hybrides en vue d'essais cliniques(2018)

Subjects
ultrasmall nanoparticles, theranostic, polysiloxane, hyphenated high-performance liquid chromatography, inductively coupled plasma mass spectrometry, General Chemical Engineering, [CHIM]Chemical Sciences, General Materials Science
Abstract

During recent decades, ultrasmall inorganic nanoparticles have attracted considerable interest due to their favorable biodistribution, pharmacokinetics and theranostic properties. In particular, AGuIX nanoparticles made of polysiloxane and gadolinium chelates were successfully translated to the clinics. In an aqueous medium, these nanoparticles are in dynamic equilibrium with polysiloxane fragments due to the hydrolysis of Si–O–Si bonds. Thanks to high-performance liquid chromatography coupled with electrospray ionization mass spectrometry, all these fragments were separated and identified.

Published
2022

7. Feasibility study and direct extraction of endogenous free metallic cations combining hemodialysis and chelating polymer

Author

Marco Natuzzi, Coralie Grange, Thomas Gréa, Thomas Brichart, Axel Aigle, Denise Bechet, Benoit Hautefeuille, Eloise Thomas, Jean-Yves Ayoub, Jeanne-Marie Bonnet, Vanessa Louzier, Bernard Allaouchiche, Aymeric Couturier, Alexandra Montembault, Paula Nunes de Oliveira, Laurent David, François Lux, Olivier Tillement, MexBrain, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Ingénierie des Matériaux Polymères (IMP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'automatique, de génie des procédés et de génie pharmaceutique (LAGEPP), Université de Lyon-Université de Lyon-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Agressions Pulmonaires et Circulatoires dans le Sepsis - UR (APCSé), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Institut Universitaire de France (IUF), and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)

Subjects
Chemistry, Medical research, Science, Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Article, Biotechnology
Abstract

In this article, we report the conception and the use of dialysis based medical device for extraction of metals. The medical device is obtained by addition in the dialysate of a functionnalized chitosan that can chelate endogenous metals like iron or copper. The water soluble functionnalized chitosan is obtained after controlled reacetylation and addition of DOTAGA. Due to the high mass of chitosan, the polymer cannot cross through the membrane and the metals are trapped in the dialysate during hemodialysis. Copper captation has been evaluated in vitro using an hemodialysis protocol. Feasibility study has been performed on healthy sheep showing no acute toxicity of the whole procedure and first insights of metallic extraction even on healthy animals.

Published
2021

8. Bi-modal photothermal/optical microscopy for complementary bio-imaging with high resolution and contrast

Author

S. V. Litvinenko, Pavlo Lishchuk, Vladimir Lysenko, Mykola Isaiev, Institute of High Technologies [Kyiv], Taras Shevchenko National University of Kyiv, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire Énergies et Mécanique Théorique et Appliquée (LEMTA ), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Materials science, Physics and Astronomy (miscellaneous), Image quality, media_common.quotation_subject, General Physics and Astronomy, FOS: Physical sciences, 02 engineering and technology, Applied Physics (physics.app-ph), 01 natural sciences, 010309 optics, [SPI]Engineering Sciences [physics], Optics, Bi modal, 0103 physical sciences, Contrast (vision), [CHIM]Chemical Sciences, Physics - Biological Physics, media_common, Quantum optics, [PHYS]Physics [physics], thermal wave method, business.industry, General Engineering, photoacoustic microscopy, Physics - Applied Physics, Photothermal therapy, 021001 nanoscience & nanotechnology, [PHYS.PHYS.PHYS-GEN-PH]Physics [physics]/Physics [physics]/General Physics [physics.gen-ph], Photothermal optical microscopy, Visualization, Biological Physics (physics.bio-ph), [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, 0210 nano-technology, business, Frequency modulation, photothermal imaging
Abstract

International audience; In the paper, combined bi-modal microscopic visualization of biological objects based on reflection-mode optical and photoacoustic measurements was presented. Gas-microphone configuration was chosen for the registration of photothermal response. Precise positioning of the scanning laser beam with modulated intensity was performed employing acousto-optic deflectors. Photoacoustic images are shown to give complementary details to the optical images obtained in the reflected light. Specifically, the photoacoustic imaging mode allows much better visualization of the features with enhanced heat localization due to the reduced heat outflow. For example, the application of the photoacoustic imaging mode was especially successful to visualize Drosophila fly's micro-hairs. Furthermore, the photoacoustic image quality was shown to be adjusted through modulation frequency.

Published
2021

9. Photothermal Effects and Heat Conduction in Nanogranular Silicon Films

Author

Zhandos N. Utegulov, Bayan A. Kurbanova, G.K. Mussabek, Vladimir Lysenko, Viktor Y. Timoshenko, Nazarbayev University [Kazakhstan], Al-Farabi Kazakh National University [Almaty] (KazNU), The National Research Nuclear University MEPhI (Moscow Engineering Physics Institute) [Moscow, Russia], Lomonosov Moscow State University (MSU), P. N. Lebedev Physical Institute of the Russian Academy of Sciences [Moscow] (LPI RAS), Russian Academy of Sciences [Moscow] (RAS), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
thin film, FDTD, General Chemical Engineering, 02 engineering and technology, Substrate (electronics), condensed_matter_physics, 01 natural sciences, photothermal, [SPI]Engineering Sciences [physics], thermal conductivity, General Materials Science, Composite material, Mussabek, Raman, [PHYS]Physics [physics], 010302 applied physics, G.K, Timoshenko, porous, nanoparticle, heat conduction, 021001 nanoscience & nanotechnology, Thermal conduction, Chemistry, B.A, symbols, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], 0210 nano-technology, Materials science, Silicon, nanostructure, phonons, chemistry.chemical_element, Z.N silicon, drop casting, Article, symbols.namesake, Thermal conductivity, void, 0103 physical sciences, [CHIM]Chemical Sciences, Thin film, QD1-999, Kurbanova, Lysenko, FEM, Phonon scattering, V, temperature, silicon, finite element modeling, nanogranular, Utegulov, laser heating, Evaporation (deposition), V.Y, Light intensity, chemistry, phase transition, Raman spectroscopy
Abstract

We present results on the photothermal (PT) and heat conductive properties of nanogranular silicon (Si) films synthesized by evaporation of colloidal droplets (drop-casting) of 100 ± 50 nm-sized crystalline Si nanoparticles (NP) deposited on glass substrates. Simulations of the absorbed light intensity and photo-induced temperature distribution across the Si NP films were carried out by using the Finite difference time domain (FDTD) and finite element mesh (FEM) modeling and the obtained data were compared with the local temperatures measured by micro-Raman spectroscopy and then was used for determining the heat conductivities k in the films of various thicknesses. The cubic-to-hexagonal phase transition in Si NP films caused by laser-induced heating was found to be heavily influenced by the film thickness and heat-conductive properties of glass substrate, on which the films were deposited. The k values in drop-casted Si nanogranular films were found to be in the range of lowest k of other types of nanostructurely voided Si films due to enhanced phonon scattering across inherently voided topology, weak NP-NP and NP-substrate interface bonding within nanogranular Si films.

Published
2021

10. Intracellular Detection and Localization of Nanoparticles by Refractive Index Measurement

Author

Géloën, Alain, Isaieva, Karyna, Isaiev, Mykola, Levinson, Olga, Berger, Emmanuelle, Lysenko, Vladimir, Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Laboratoire Énergies et Mécanique Théorique et Appliquée (LEMTA ), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Ray Techniques Ltd., Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), European Project: 690945,H2020,H2020-MSCA-RISE-2015,CARTHER(2016), VIDAL, Armelle, and Carbon-based nano-materials for theranostic application - CARTHER - - H20202016-01-01 - 2019-12-31 - 690945 - VALID

Subjects
[PHYS]Physics [physics], refractive index, [SPI] Engineering Sciences [physics], quantitative image analysis, Communication, Chemical technology, nanoparticle, single cell analysis, TP1-1185, [PHYS] Physics [physics], Nanodiamonds, Refractometry, [SPI]Engineering Sciences [physics], real-time analysis, [CHIM] Chemical Sciences, Nanoparticles, [CHIM]Chemical Sciences, label-free imaging, digital holographic microscope
Abstract

International audience; The measuring of nanoparticle toxicity faces an important limitation since it is based on metrics exposure, the concentration at which cells are exposed instead the true concentration inside the cells. In vitro studies of nanomaterials would benefit from the direct measuring of the true intracellular dose of nanoparticles. The objective of the present study was to state whether the intracellular detection of nanodiamonds is possible by measuring the refractive index. Based on optical diffraction tomography of treated live cells, the results show that unlabeled nanoparticles can be detected and localized inside cells. The results were confirmed by fluorescence measurements. Optical diffraction tomography paves the way to measuring the true intracellular concentrations and the localization of nanoparticles which will improve the dose-response paradigm of pharmacology and toxicology in the field of nanomaterials.

Published
2021

11. Quantitative Tissue Pharmacokinetics and EPR Effect of AGuIX Nanoparticles: A Multimodal Imaging Study in an Orthotopic Glioblastoma Rat Model and Healthy Macaque

Author

Bertrand Kuhnast, Charles Truillet, Xavier Maître, Michael J. Evans, Olivier Tillement, Katalin Selmeczi, Claude Comtat, Vu-Long Tran, François Lux, Sebastien Jan, Nicolas Tournier, Benoit Jego, Maria Anisorac, Université Paris-Saclay, Laboratoire d’imagerie biomédicale multimodale [Orsay] (BioMaps), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unite de recherche en résonance magnétique médicale (U2R2M), Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre-Centre National de la Recherche Scientifique (CNRS), Laboratoire Lorrain de Chimie Moléculaire (L2CM), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, STMicroelectronics, University of California [San Francisco] (UCSF), University of California, PhotoNS, LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of California [San Francisco] (UC San Francisco), and University of California (UC)

Subjects
Gadolinium, Biomedical Engineering, Contrast Media, Pharmaceutical Science, chemistry.chemical_element, Nanoparticle, Multimodal Imaging, Macaque, Biomaterials, [SPI]Engineering Sciences [physics], Nuclear magnetic resonance, Pharmacokinetics, In vivo, biology.animal, Radioresistance, medicine, Animals, Humans, [CHIM]Chemical Sciences, [PHYS]Physics [physics], medicine.diagnostic_test, biology, Magnetic Resonance Imaging, In vitro, Rats, 3. Good health, chemistry, Positron emission tomography, Macaca, Nanoparticles, Glioblastoma
Abstract

International audience; AGuIX are emerging radiosensitizing nanoparticles (NPs) for precision radiotherapy (RT) under clinical evaluation (Phase 2). Despite being accompanied by MRI thanks to the presence of gadolinium (Gd) at its surface, more sensitive and quantifiable imaging technique should further leverage the full potential of this technology. In this study, it is shown that Zr-89 can be labeled on such NPs directly for positron emission tomography (PET) imaging with a simple and scalable method. The stability of such complexes is remarkable in vitro and in vivo. Using a glioblastoma orthotopic rat model, it is shown that injected Zr-89-AGuIX is detectable inside the tumor for at least 1 week. Interestingly, the particles seem to efficiently infiltrate the tumor even in necrotic areas, which places great hope for the treatment of radioresistant tumor. Lastly, the first PET/MR whole-body imaging is performed in non-human primate (NHP), which further demonstrates the translational potential of these bimodal NP.

Published
2021

12. Quantifying nanotherapeutic penetration using hydrogel based microsystem as a new 3D in vitro platform

Author

Olivier Tillement, Ting-Di Wu, Jean-Luc Guerquin-Kern, Sandrine Lacombe, Saba Goodarzi, Charlotte Rivière, Audrey Prunet, Hélène Delanoë-Ayari, Erika Porcel, Guillaume Bort, Fabien Rossetti, François Lux, Biophysique (BIOPHYSIQUE), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
Fluorescence-lifetime imaging microscopy, Microfluidics, Biomedical Engineering, Bioengineering, 02 engineering and technology, Biochemistry, law.invention, 03 medical and health sciences, chemistry.chemical_compound, [SPI]Engineering Sciences [physics], In vivo, Confocal microscopy, law, Microsystem, [CHIM]Chemical Sciences, 030304 developmental biology, [PHYS]Physics [physics], 0303 health sciences, In vitro toxicology, Spheroid, General Chemistry, 021001 nanoscience & nanotechnology, chemistry, Agarose, 0210 nano-technology, Biomedical engineering
Abstract

International audience; Abstract The huge gap between 2D in vitro assays used for drug screening, and the in vivo 3D-physiological environment hampered reliable predictions for the route and accumulation of nanotherapeutics in vivo. For such nanotherapeutics, Multi-Cellular Tumour Spheroids (MCTS) is emerging as a good alternative in vitro model. However, the classical approaches to produce MCTS suffer from low yield, slow process, difficulties in MCTS manipulation and compatibility with high-magnification fluorescent optical microscopy. On the other hand, spheroid-on-chip set-ups developed so far require a microfluidic practical knowledge difficult to transfer to a cell biology laboratory. We present here a simple yet highly flexible 3D-model microsystem consisting of agarose-based microwells. Fully compatible with the multi-well plates format conventionally used in cell biology, our simple process enables the formation of hundreds of reproducible spheroids in a single pipetting. Immunostaining and fluorescent imaging including live high-resolution optical microscopy can be performed in-situ , with no manipulation of spheroids. As a proof-of-principle of the relevance of such in vitro platform for nanotherapeutics evaluation, this study investigates the kinetic and localization of nanoparticles within colorectal cancer MCTS cells (HCT-116). The nanoparticles chosen are sub-5 nm ultrasmall nanoparticles made of polysiloxane and gadolinium chelates that can be visualized in MRI (AGuIX ® , currently implicated in clinical trials as effective radiosensitizers for radiotherapy) and confocal microscopy after addition of Cy 5.5. We show that the amount of AGuIX ® nanoparticles within cells is largely different in 2D and 3D. Using our flexible agarose-based microsystems, we are able to resolve spatially and temporally the penetration and distribution of AGuIX ® nanoparticles within MCTS. The nanoparticles are first found in both extracellular and intracellular space of MCTS. While the extracellular part is washed away after few days, we evidenced intracellular localisation of AGuIX ® , mainly within lysosomes compartment, but also occasionally within mitochondria. Our agarose-based microsystem appears hence as a promising 3D in vitro user-friendly platform for investigation of nanotherapeutics transport, ahead of in vivo studies. Abstract Figure Graphical abstract

Published
2021

13. Three‐dimensional quantitative MRI of aerosolized gadolinium‐based nanoparticles and contrast agents in isolated ventilated porcine lungs

Author

Olivier Tillement, Noël Pinaud, Bei Zhang, Sophie Perinel, Yannick Crémillieux, François Lux, Nobuyasu Ichinose, Marco Natuzzi, Vi Pham, Jérémie Pourchez, Yoann Montigaud, Clémence Bal, Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Canon Medical Systems Corporation

Subjects
Materials science, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Swine, media_common.quotation_subject, Gadolinium, Contrast Media, chemistry.chemical_element, Nanoparticle, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Imaging, Three-Dimensional, 0302 clinical medicine, medicine, Animals, Humans, Contrast (vision), Radiology, Nuclear Medicine and imaging, Lung, ComputingMilieux_MISCELLANEOUS, Aerosolization, media_common, Echo time, respiratory system, Magnetic Resonance Imaging, Nebulizer, medicine.anatomical_structure, chemistry, Homogeneous, Nanoparticles, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 030217 neurology & neurosurgery, Biomedical engineering
Abstract

International audience; PurposeThe objective of this study is to evaluate the suitability and performance of ultra‐short echo time (UTE) sequences for imaging and quantifying the deposition of nebulized MRI contrast agents in human‐sized lungs.MethodsNebulization of clinically used contrast agent or gadolinium‐based nanoparticles were performed using a commercial jet nebulizer in isolated and ventilated porcine lungs connected to a 3D‐printed human upper airways replica. MR images of isolated lungs were acquired on a 3T clinical MR scanner using 3D UTE sequences at different flip angles.Results3D acquisitions with isotropic millimetric resolution were obtained in less than 4 min. Images exhibit homogeneous and large MR signal enhancement (above 200%) following nebulization of both types of aerosols. Deposition of aerosol down to the level of the bronchi of secondary lobules was visualized. T1 values and the concentration of nanoparticles obtained by MRI were found to correlate with the amount of nebulized gadolinium3+ ions.ConclusionThe distribution of aerosolized gadolinium‐based contrast agent or nanoparticles can be visualized and quantified using UTE MRI in large animal ventilated lung model on a clinical MRI scanner. This protocol can be used for assessing and quantifying aerosol regional deposition with high spatial resolution (1 mm 3D isotropic) without ionizing radiation and could be applied in the future for diagnostic or therapeutic applications in patients.

Published
2019

14. Inelastic Light Scattering by Multiple Vibrational Modes in Individual Gold Nanodimers

Author

Adrien Girard, Alain Mermet, Emmanuel Cottancin, Jean Lermé, Jérémie Margueritat, Aurélien Crut, Hélène Gehan, Christophe Bonnet, Spectroscopies optiques des matériaux verres, amorphes et à nanoparticules (SOPRANO), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Agrégats et nanostructures (AGNANO), Formation, élaboration de nanomatériaux et cristaux (FENNEC), FemtoNanoOptics (FemtoNanoOptics), and Luminescence (LUMINESCENCE)

Subjects
Materials science, genetic structures, Physics::Optics, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Molecular physics, Light scattering, Scattering, Physics::Atomic and Molecular Clusters, Single-particle experiments, Physical and Theoretical Chemistry, Spectroscopy, [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], Mode (statistics), 021001 nanoscience & nanotechnology, Optomechanics, Nanomechanics, eye diseases, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Oscillation, General Energy, Acoustic coupling, Oligomers, Molecular vibration, Raman spectroscopy, Nanoparticles, sense organs, 0210 nano-technology, Nanospheres
Abstract

International audience; To be Raman-active (or, more generally, detectable using optical spectroscopy techniques), a vibrational mode of a nanosystem has to modulate its optical response. For small, isolated nanospheres, this is the case for only two categories of vibrational modes, namely, quadrupolar and radial ones. However, assembling nanospheres as dimers makes additional modes Raman-active, as previously demonstrated by the detection in the ultralow frequency range of a hybridized quasi-translation mode in previous measurements on single and ensembles of gold nanosphere dimers. In the present work, we use our recently developed single-particle Raman spectroscopy setup to compare inelastic light scattering by single isolated and dimerized gold nanospheres in an extended frequency range (0–40 GHz). The Raman spectra acquired on isolated nanoparticles present a single peak associated with their fundamental quadrupolar mode, consistently with previous ensemble measurements. In contrast, the spectra measured on dimers are richer and display a number of peaks increasing with decreasing interparticle distance, with all l = 2–8 Lamb modes detected in the quasi-contact case. These observations are rationalized using a recently developed classical model of inelastic light scattering by nanospheres. Importantly, our modeling approach takes into account the real electric field within the nanoparticles (computed using standard or generalized Mie theories) instead of relying on the frequently used Born and quasistatic approximations. This ingredient appears decisive for reaching a qualitative understanding of the measured spectra, explaining in particular the dominance of the l = 2 quadrupolar mode for isolated spheres and the increasing contribution of higher-order modes for increasing electromagnetic interactions in nanosphere dimers.

Published
2019

15. Terbium-Based AGuIX-Design Nanoparticle to Mediate X-ray-Induced Photodynamic Therapy

Author

Daouk, Joël, Iltis, Mathilde, Dhaini, Batoul, Béchet, Denise, Arnoux, Philippe, Rocchi, Paul, Delconte, Alain, Habermeyer, Benoît, Lux, François, Frochot, Céline, Tillement, Olivier, Barberi-Heyob, Muriel, Schohn, Hervé, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Laboratoire Réactions et Génie des Procédés (LRGP), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Porphychem Company (PorphyChem SAS), European Project: 321570,EC:FP7:NMP,FP7-ERANET-2012-RTD,EURONANOMED II(2012), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
AGuIX ®, terbium, [SDV.CAN]Life Sciences [q-bio]/Cancer, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Article, singlet oxygen, X-ray-induced photodynamic therapy, RS1-441, AGuIX®, terbium, glioblastoma multiforme, Pharmacy and materia medica, photodynamic therapy, Medicine, AGuIX®, [CHIM.COOR]Chemical Sciences/Coordination chemistry, gadolinium, X-rayinduced photodynamic therapy
Abstract

International audience; X-ray-induced photodynamic therapy is based on the energy transfer from a nanoscintillator to a photosensitizer molecule, whose activation leads to singlet oxygen and radical species generation, triggering cancer cells to cell death. Herein, we synthesized ultra-small nanoparticle chelated with Terbium (Tb) as a nanoscintillator and 5-(4-carboxyphenyl succinimide ester)-10,15,20-triphenyl porphyrin (P1) as a photosensitizer (AGuIX@Tb-P1). The synthesis was based on the AGuIX@ platform design. AGuIX@Tb-P1 was characterised for its photo-physical and physico-chemical properties. The effect of the nanoparticles was studied using human glioblastoma U-251 MG cells and was compared to treatment with AGuIX@ nanoparticles doped with Gadolinium (Gd) and P1 (AguIX@Gd-P1). We demonstrated that the AGuIX@Tb-P1 design was consistent with X-ray photon energy transfer from Terbium to P1. Both nanoparticles had similar dark cytotoxicity and they were absorbed in a similar rate within the cells. Pre-treated cells exposure to X-rays was related to reactive species production. Using clonogenic assays, establishment of survival curves allowed discrimination of the impact of radiation treatment from X-ray-induced photodynamic effect. We showed that cell growth arrest was increased (35%-increase) when cells were treated with AGuIX@Tb-P1 compared to the nanoparticle doped with Gd

Published
2021

16. Unique features of brain metastases-targeted AGuIX nanoparticles vs their constituents: A focus on glutamate-/GABA-ergic neurotransmission in cortex nerve terminals

Author

Konstantin Paliienko, François Lux, Serhiy Komisarenko, Artem Pastukhov, Natalia Pozdnyakova, Natalia Krisanova, Valeria Grytsaenko, Paul Rocchi, Vladimir Lysenko, Olivier Tillement, Marina Dudarenko, Tatiana Borisova, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, National Academy of Sciences of Ukraine (NASU), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Radiation-Sensitizing Agents, Glutamic Acid, Gadolinium, Pharmacology, Neurotransmission, Toxicology, Inhibitory postsynaptic potential, Synaptic Transmission, Exocytosis, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0404 agricultural biotechnology, Animals, [CHIM]Chemical Sciences, Rats, Wistar, gamma-Aminobutyric Acid, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Membrane potential, Cerebral Cortex, [PHYS]Physics [physics], 0303 health sciences, Dose-Response Relationship, Drug, Chemistry, Brain Neoplasms, Glutamate receptor, Transporter, 04 agricultural and veterinary sciences, General Medicine, 040401 food science, 3. Good health, Cortex (botany), Rats, Excitatory postsynaptic potential, Nanoparticles, Food Science
Abstract

Gadolinium-based radiosensitizing AGuIX nanoparticles (AGuIX) currently tested two phase 2 clinical trials in association with radiotherapy for the treatment of brain metastases. Here, excitatory/inhibitory neurotransmission was assessed in rat cortex nerve terminals in the presence of AGuIX and their constituents (DOTAGA and DOTAGA/Gd3+) at concentrations used for medical treatment, and those 5–24 times higher. The ambient level, transporter-mediated, tonic and exocytotic release of L-[14C]glutamate and [3H]GABA, the membrane potential of nerve terminals were not changed in the presence of AGuIX at concentrations used for medical treatment ([Gd3+] = 0.25 mM, corresponding to 0.25 g.L−1), and DOTAGA (0.25 mM) and DOTAGA/Gd3+ (0.25 mM/0.01 mM). Difference between AGuIX and the precursors was uncovered, when their concentrations were increased. AGuIX (1.25–6 mM) did not change any transport characteristics of L-[14C]glutamate and [3H]GABA, whereas, DOTAGA (1.25–6 mM) affected the membrane potential, ambient level, and exocytotic release of L-[14C]glutamate and [3H]GABA. Gd3+ did not mask, but even enhanced above effects of DOTAGA. Therefore, AGuIX did not influence glutamate- and GABA-ergic neurotransmission at the presynaptic site. In contrast, DOTAGA and mixture DOTAGA/Gd3+ significantly affected synaptic neurotransmission at high concentrations. AGuIX own structure that overcomes neurotoxic features of their constituents.

Published
2021

17. Rapid Evaluation of Novel Therapeutic Strategies Using a 3D Collagen-Based Tissue-Like Model

Author

Adrien Mau, Pauline Maury, Erika Porcel, Sandrine Lacombe, Olivier Tillement, Marie-Claire Schanne-Klein, François Lux, Pierre Mahou, Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), VIDAL, Armelle, Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, collagen, Histology, [SPI] Engineering Sciences [physics], lcsh:Biotechnology, Cell, Biomedical Engineering, Bioengineering, Matrix (biology), SHG, [PHYS] Physics [physics], Extracellular matrix, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, Single-cell analysis, In vivo, lcsh:TP248.13-248.65, [CHIM] Chemical Sciences, medicine, Methods, [CHIM]Chemical Sciences, Clonogenic assay, [PHYS]Physics [physics], Chemistry, 3D cell model, nanoagents, radioenhancement, Bioengineering and Biotechnology, 3. Good health, internalization, 030104 developmental biology, medicine.anatomical_structure, Homogeneous, Cell culture, 030220 oncology & carcinogenesis, Biophysics, hydrogel, radiosensitization, Biotechnology
Abstract

2D cell cultures are commonly used to rapidly evaluate the therapeutic potential of various treatments on living cells. However, the effects of the extracellular matrix (ECM) including the 3D arrangement of cells and the complex physiology of native environment are missing, which makes these models far from in vivo conditions. 3D cell models have emerged in preclinical studies to simulate the impact of the ECM and partially bridge the gap between monolayer cultures and in vivo tissues. To date, the difficulty to handle the existing 3D models, the cost of their production and their poor reproducibility have hindered their use. Here, we present a reproducible and commercially available “3D cell collagen-based model” (3D-CCM) that allows to study the influence of the matrix on nanoagent uptake and radiation effects. The cell density in these samples is homogeneous. The oxygen concentration in the 3D-CCM is tunable, which opens the opportunity to investigate hypoxic effects. In addition, thanks to the intrinsic properties of the collagen, the second harmonic imaging microscopy may be used to probe the whole volume and visualize living cells in real-time. Thus, the architecture and composition of 3D-CCMs as well as the impact of various therapeutic strategies on cells embedded in the ECM is observed directly. Moreover, the disaggregation of the collagen matrix allows recovering of cells without damaging them. It is a major advantage that makes possible single cell analysis and quantification of treatment effects using clonogenic assay. In this work, 3D-CCMs were used to evaluate the correlative efficacies of nanodrug exposure and medical radiation on cells contained in a tumor like sample. A comparison with monolayer cell cultures was performed showing the advantageous outcome and the higher potential of 3D-CCMs. This cheap and easy to handle approach is more ethical than in vivo experiments, thus, giving a fast evaluation of cellular responses to various treatments., Graphical Abstract 3D cell collagen-based model with tunable environment conditions (oxygen concentration, nanodrug exposure or irradiations).

Published
2021

18. Impact of Carbon Fluoroxide Nanoparticles on Cell Proliferation

Author

Tetiana Serdiuk, Sergei Alekseev, G.K. Mussabek, Alexander Yu. Kharin, Alain Géloën, Vladimir Lysenko, Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Al-Farabi Kazakh National University [Almaty] (KazNU), The National Research Nuclear University MEPhI (Moscow Engineering Physics Institute) [Moscow, Russia], Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Taras Shevchenko National University of Kyiv, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and European Project: 690945,H2020,H2020-MSCA-RISE-2015,CARTHER(2016)

Subjects
inorganic chemicals, Cell type, Biocompatibility, nanoparticles, cellular uptake, cytotoxicity, cancer cells, xCELLigence, General Chemical Engineering, Cell, education, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Article, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], mental disorders, medicine, Cytotoxic T cell, General Materials Science, Cytotoxicity, QD1-999, cancer cell, health care economics and organizations, Cell growth, Chemistry, technology, industry, and agriculture, [CHIM.MATE]Chemical Sciences/Material chemistry, respiratory system, 021001 nanoscience & nanotechnology, 0104 chemical sciences, medicine.anatomical_structure, Cell culture, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Cancer cell, Biophysics, 0210 nano-technology
Abstract

Cytotoxicity of fluorescent carbon fluoroxide (CFO) nanoparticles (NPs) was studied in a label-free manner on several cancer and non-cancer cell lines. A direct cytotoxic effect of the CFO NPs was clearly observed by a suppression of cell proliferation. The real-time measurement of cell activities allowed to quantify the impact of the uptaken NPs on cell proliferation and after washout of the NPs from the cell culture medium. The results show more toxic effects of the CFO NPs on cancer than on non-cancer cell lines. The notion of NPs biocompatibility must be related to a maximum concentration value of the NPs acceptable for a given cell type. Furthermore, the cytotoxicity effects of NPs should be studied not only during their direct exposure to cells but also after their washout from the culture medium., Nanoletters, 11 (12), ISSN:2079-4991

Published
2021

19. Biodegradation of metal-based ultra-small nanoparticles: A combined approach using TDA-ICP-MS and CE-ICP-MS

Author

Olivier Tillement, Agnès Hagège, Tristan Doussineau, François Lux, Hervé Cottet, Lucie Labied, Jérôme Randon, Paul Rocchi, Separative Methods - Techniques séparatives, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, NH TherAguix SA [Meylan], Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)

Subjects
Taylor dispersion analysis, Gadolinium, Contrast Media, Metal Nanoparticles, chemistry.chemical_element, Nanoparticle, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Biochemistry, Mass Spectrometry, Analytical Chemistry, Metal, Capillary electrophoresis, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Environmental Chemistry, Inductively coupled plasma mass spectrometry, Dissolution, Ultrasmall nanoparticles, Spectroscopy, Chromatography, Electrophoresis, Capillary, [CHIM.MATE]Chemical Sciences/Material chemistry, Biodegradation, 021001 nanoscience & nanotechnology, Combined approach, 0104 chemical sciences, Gadolinium containing drug, chemistry, visual_art, visual_art.visual_art_medium, Nanoparticles, 0210 nano-technology
Abstract

International audience; The knowledge of the fate of metal-containing nanoparticles in biological media in aqueous media is of utmost importance for the future use of these promising theranostic agents for clinical applications. A methodology based on the combination of TDA-ICP-MS and CE-ICP-MS was applied to study the degradation pathway of AGuIX, a phase 2 clinical ultrasmall gadolinium-containing nanoparticle. Nanoparticle size measurements and gadolinium speciation performed in different media (phosphate buffer, urine and serum) demonstrated an accelerated dissolution of AGuIX in serum, without any release of free gadolinium for each medium.

Published
2021

20. Taylor dispersion analysis coupled to ICP-MS for ultrasmall nano-particle size measurement: from drug product to biological media studies

Author

Labied, Lucie, Rocchi, Paul, Doussineau, Tristan, Randon, Jérôme, Tillement, Olivier, Lux, François, Hagège, Agnès, Separative Methods - Techniques séparatives, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, NH TherAguix SA [Meylan], Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), This work has been supported by a French Government Grant managed by the French National Research Agency (ANR-18-CE17-0025-02)., and ANR-18-CE17-0025,ANALYTAGUIX,Caractérisation analytique de nanoparticules hybrides en vue d'essais cliniques(2018)

Subjects
[CHIM]Chemical Sciences, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract

The authors would like to thank Mexbrain for providing the cerebrospinal fluid.; International audience; During last decade, special focus has been laid on ultrasmall nanoparticles for nanomedicine and eventual clinical translation. To achieve such translation, a lot of challenges have to be solved. Among them, size determination is a particularly tricky one. In this aim, we have developed a simple hyphenation between Taylor dispersion analysis and ICP-MS. This method was proven to allow the determination of the hydrodynamic radius of metal-containing nanoparticles, even for sizes under 5 nm, with a relative standard deviation below 10% (with a 95% confidence interval) and at low concentrations. Moreover, its specificity provides the opportunity to perform measurements in complex biological media. This was applied to the characterization of an ultrasmall gadolinium-containing nanoparticle, used as theranostic agent in cancer diseases. Hydrodynamic radii measured in urine, cerebrospinal fluid and undiluted serum demonstrated the absence of interaction between the particle and biological compounds such as proteins.

Published
2021

21. Preparation and characterization of F-, O-, and N-containing carbon nanoparticles for pH sensing

Author

Nazym Zhylkybayeva, Vladyslav V. Lisnyak, Valeriy A. Skryshevsky, Yerzhan T. Taurbayev, Volodymyr Lysenko, G.K. Mussabek, Ruslan Mariychuk, Oksana Yu. Tananiko, Alexander N. Zaderko, Olga Yu. Boldyrieva, Taras Shevchenko National University of Kyiv, University of Prešov, Institute of High Technologies [Kyiv], Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institute of Information and Computational Technologies (IICT), and Al-Farabi Kazakh National University [Almaty] (KazNU)

Subjects
and N-containing carbon NPs, O, Materials Science (miscellaneous), Solvothermal synthesis, chemistry.chemical_element, Nanochemistry, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, chemistry.chemical_compound, symbols.namesake, [SPI]Engineering Sciences [physics], pH nanosensors, [CHIM]Chemical Sciences, Electrical and Electronic Engineering, Physical and Theoretical Chemistry, Fourier transform infrared spectroscopy, Photoluminescence, ComputingMilieux_MISCELLANEOUS, [PHYS]Physics [physics], Trifluoromethyl, Thermal decomposition, Cell Biology, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, Atomic and Molecular Physics, and Optics, 0104 chemical sciences, chemistry, 13. Climate action, F, symbols, Fluorine, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], 0210 nano-technology, Raman spectroscopy, Carbon, Biotechnology, Nuclear chemistry
Abstract

International audience; A novel sensing system was designed for pH measurements based on the enhanced and quenched photoluminescence (PL) and UV–Vis absorption of the diluted water solutions of F-, O-, and N-containing carbon nanoparticles (FON-CNPs). These FON-CNPs were solvothermally synthesized, dissolved, ultra-filtrated, and separated by thin-layer chromatography. The total fluorine content in them was found to be 1.2–1.5 mmol per gram. Their TGA showed a total weight loss of 52.7% because of the thermal decomposition and detachment of the surface groups and the partial burning of the functionalized shell on the carbon core at temperatures below 1200 °C. TEM and Raman data confirmed the presence of graphitic structures in the carbon core. From the results of ATR FTIR and UV–Vis spectroscopies, we showed that a carbon shell incorporates different functional groups covering the carbon core. The surface groups of the carbon shell include carboxyl, phenolic, and carbonyl groups. Heterocyclic N-containing and amino groups and trifluoromethyl groups supporting the hydrophobicity were also found. We suggested the possible reasons for the pH responses obtained with the sensing system considering them dependent on the de-protonation of functional groups with pH change.

Published
2021

22. 3D Spatial Distribution of Nanoparticles in Mice Brain Metastases by X-ray Phase-Contrast Tomography

Author

Longo, Elena, Sancey, Lucie, Cedola, Alessia, Barbier, Emmanuel L., Bravin, Alberto, Brun, Francesco, Bukreeva, Inna, Fratini, Michela, Massimi, Lorenzo, Greving, Imke, Le Duc, Geraldine, Tillement, Olivier, De La Rochefoucauld, Ombeline, Zeitoun, Philippe, Helmholtz-Zentrum Hereon, Laboratoire d'optique appliquée (LOA), École Nationale Supérieure de Techniques Avancées (ENSTA Paris)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Consiglio Nazionale delle Ricerche [Roma] (CNR), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), European Synchrotron Radiation Facility (ESRF), P. N. Lebedev Physical Institute of the Russian Academy of Sciences [Moscow] (LPI RAS), Russian Academy of Sciences [Moscow] (RAS), Department of Medical Physics and Biomedical Engineering (UCL), University College of London [London] (UCL), NH TherAguix SA [Meylan], Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Imagine Optic, ANR-11-INBS-0006,FLI,France Life Imaging(2011), European Project: 665207,H2020,H2020-FETOPEN-2014-2015-RIA,VOXEL(2015), Longo, E., Sancey, L., Cedola, A., Barbier, E. L., Bravin, A., Brun, F., Bukreeva, I., Fratini, M., Massimi, L., Greving, I., Le Duc, G., Tillement, O., De La Rochefoucauld, O., Zeitoun, P., Longo, E, Sancey, L, Cedola, A, Barbier, E, Bravin, A, Brun, F, Bukreeva, I, Fratini, M, Massimi, L, Greving, I, Le Duc, G, Tillement, O, De La Rochefoucauld, O, Zeitoun, P, VIDAL, Armelle, Infrastructures - France Life Imaging - - FLI2011 - ANR-11-INBS-0006 - INBS - VALID, volumetric medical x-ray imaging at extremely low dose - VOXEL - - H20202015-06-01 - 2019-05-31 - 665207 - VALID, and National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR)

Subjects
inorganic chemicals, Cancer Research, melanoma metastase, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, synchrotron radiation, nanoparticle, brain, education, technology, industry, and agriculture, FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA), [SDV.CAN]Life Sciences [q-bio]/Cancer, X-ray phase-contrast tomography, respiratory system, 3D visualization, melanoma metastases, nanoparticles, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, mental disorders, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], health care economics and organizations, Original Research
Abstract

International audience; Characterizing nanoparticles (NPs) distribution in multiple and complex metastases is of fundamental relevance for the development of radiological protocols based on NPs administration. In the literature, there have been advances in monitoring NPs in tissues. However, the lack of 3D information is still an issue. X-ray phase-contrast tomography (XPCT) is a 3D label-free, non-invasive and multi-scale approach allowing imaging anatomical details with high spatial and contrast resolutions. Here an XPCT qualitative study on NPs distribution in a mouse brain model of melanoma metastases injected with gadolinium-based NPs for theranostics is presented. For the first time, XPCT images show the NPs uptake at micrometer resolution over the full brain. Our results revealed a heterogeneous distribution of the NPs inside the melanoma metastases, bridging the gap in spatial resolution between magnetic resonance imaging and histology. Our findings demonstrated that XPCT is a reliable technique for NPs detection and can be considered as an emerging method for the study of NPs distribution in organs.

Published
2021

23. Enhanced MRI-guided radiotherapy with gadolinium-based nanoparticles: preclinical evaluation with an MRI-linac

Author

N. M. Holmes, Alexander James, Tara L. Roberts, Olivier Tillement, G. Le Duc, Bin Dong, Zdenka Kuncic, Urszula Jelen, François Lux, H L Byrne, Gary P Liney, School of Physics [Sydney], The University of Sydney, NH TherAguix SA [Meylan], Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), University of New South Wales [Sydney] (UNSW), Ingham Institute for Applied Medical Research [Liverpool, NSW, Australia], School of Medicine [Western Sydney University], and Western Sydney University

Subjects
Gadolinium, medicine.medical_treatment, Biomedical Engineering, Pharmaceutical Science, chemistry.chemical_element, Nanoparticle, lcsh:RC254-282, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Tumour tissue, [SPI]Engineering Sciences [physics], 0302 clinical medicine, medicine, [CHIM]Chemical Sciences, Physical and Theoretical Chemistry, [PHYS]Physics [physics], Mri linac, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Mr contrast, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Radiation therapy, Oncology, chemistry, 030220 oncology & carcinogenesis, Mri guided radiotherapy, Nuclear medicine, business
Abstract

Background The AGuIX® (NH TherAguix) nanoparticle has been developed to enhance radiotherapy treatment and provide strong MR contrast. These two properties have previously been investigated separately and progressed to clinical trial following a clinical workflow of separate MR imaging followed some time later by radiotherapy treatment. The recent development of MRI-linacs (combined Magnetic Resonance Imaging–linear accelerator systems enabling MRI-guided radiotherapy) opens up a new workflow where MR confirmation of nanoparticle uptake can be carried out at the time of treatment. A preclinical study was carried out to assess the suitability of a gadolinium-containing nanoparticle AGuIX® (NH TherAguix) for nano-enhanced image-guided radiotherapy on an MRI-linac. Methods Treatments were carried out on F344 Fischer rats bearing a 9L glioma brain tumour. Animals received either: (A) no treatment; (B) injection of nanoparticles followed by MRI; (C) radiotherapy with MRI; or (D) injection of nanoparticles followed by radiotherapy with MRI. Pre-clinical irradiations were carried out on the 1.0 T, 6 MV in-line Australian MRI-linac. Imaging used a custom head coil specially designed to minimise interference from the radiotherapy beam. Anaesthetised rats were not restrained during treatment but were monitored with a cine-MRI sequence. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis was used to quantify residual gadolinium in the brain in normal and tumour tissue. Results A preclinical evaluation of nano-enhanced radiation treatment has been carried out on a 1.0 T MRI-linac, establishing a workflow on these novel systems. Extension of life when combining radiotherapy with nanoparticles was not statistically different from that for rats receiving radiotherapy only. However, there was no detrimental effect for animals receiving nanoparticles and radiation treatment in the magnetic field compared with control branches. Cine-MR imaging was sufficient to carry out monitoring of anaesthetised animals during treatment. AGuIX nanoparticles demonstrated good positive contrast on the MRI-linac system allowing confirmation of tumour extent and nanoparticle uptake at the time of treatment. Conclusions Novel nano-enhanced radiotherapy with gadolinium-containing nanoparticles is ideally suited for implementation on an MRI-linac, allowing a workflow with time-of-treatment imaging. Live irradiations using this treatment workflow, carried out for the first time at the Australian MRI-linac, confirm the safety and feasibility of performing MRI-guided radiotherapy with AGuIX® nanoparticles. Follow-up studies are needed to demonstrate on an MRI-linac the radiation enhancement effects previously shown with conventional radiotherapy.

Published
2020

24. Multiscale selectivity and in vivo biodistribution of NRP-1-targeted theranostic AGuIX nanoparticles for PDT of glioblastoma

Author

Gries, Mickaël, Thomas, Noémie, Daouk, Joël, Rocchi, Paul, Choulier, Laurence, Jubréaux, Justine, Pierson, Julien, Reinhard, Aurélie, Jouan-Hureaux, Valérie, Chateau, Alicia, Acherar, Samir, Frochot, Céline, Lux, François, Tillement, Olivier, Barberi-Heyob, Muriel, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Laboratoire de Chimie Physique Macromoléculaire (LCPM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), and Laboratoire Réactions et Génie des Procédés (LRGP)

Subjects
Porphyrins, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, glioblastoma, Endothelial Cells, Gadolinium, vascular photodynamic therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, AGuIX nanoparticle, radiation therapies, Neuropilin-1, Theranostic Nanomedicine, peptide, Rats, Photochemotherapy, Animals, Humans, Nanoparticles, NRP-1, brain tumors, Tissue Distribution, Molecular Targeted Therapy, Neoplasm Metastasis, Precision Medicine, Original Research
Abstract

International audience; Background: Local recurrences of glioblastoma (GBM) after heavy standard treatments remain frequent and lead to a poor prognostic. Major challenges are the infiltrative part of the tumor tissue which is the ultimate cause of recurrence. The therapeutic arsenal faces the difficulty of eradicating this infiltrating part of the tumor tissue while increasing the targeting of tumor and endogenous stromal cells such as angiogenic endothelial cells. In this aim, neuropilin-1 (NRP-1), a transmembrane receptor mainly overexpressed by endothelial cells of the tumor vascular system and associated with malignancy, proliferation and migration of GBM, highlighted to be a relevant molecular target to promote the anti-vascular effect of photodynamic therapy (VTP).Methods: The multiscale selectivity was investigated for KDKPPR peptide moiety targeting NRP-1 and a porphyrin molecule as photosensitizer (PS), both grafted onto original AGuIX design nanoparticle. AGuIX nanoparticle, currently in Phase II clinical trials for the treatment of brain metastases with radiotherapy, allows to achieve a real-time magnetic resonance imaging (MRI) and an accumulation in the tumor area by EPR (enhanced permeability and retention) effect. Using surface-plasmon resonance (SPR), we evaluated the affinities of KDKPPR and scramble free peptides, and also peptides-conjugated AGuIX nanoparticles to recombinant rat and human NRP-1 proteins. For in vivo selectivity, we used a cranial window model and parametric maps obtained from T2*-weighted perfusion MRI analysis.Results: The photophysical characteristics of the PS and KDKPPR molecular affinity for recombinant human NRP-1 proteins were maintained after the functionalization of AGuIX nanoparticle with a dissociation constant of 4.7 μM determined by SPR assays. Cranial window model and parametric maps, both revealed a prolonged retention in the vascular system of human xenotransplanted GBM. Thanks to the fluorescence of porphyrin by non-invasive imaging and the concentration of gadolinium evaluated after extraction of organs, we checked the absence of nanoparticle in the brains of tumor-free animals and highlighted elimination by renal excretion and hepatic metabolism.Conclusion: Post-VTP follow-ups demonstrated promising tumor responses with a prolonged delay in tumor growth accompanied by a decrease in tumor metabolism.

Published
2020

25. Roadmap for metal nanoparticles in radiation therapy: current status, translational challenges, and future directions

Author

Karl T. Butterworth, Yaser Hadi Gholami, Kyle Bromma, Vincent Favaudon, Zdenka Kuncic, Jason R. Cook, Udoka Ibeh, Stéphane Lucas, Stephen J. McMahon, E. Gargioni, Sandrine Lacombe, Kevin M. Prise, Anne-Catherine Heuskin, Léon Sanche, Yaroslav Stanishevskiy, Olivier Tillement, Bijay Singh, Henry M. Smilowitz, Sang Hyun Cho, J Donald Payne, Needa A. Virani, Erika Porcel, Ross Berbeco, Wonmo Sung, Félicien Hespeels, Benedikt Rudek, Dmitry Nevozhay, Wassana Yantasee, Hans Rabus, Devika B. Chithrani, Wilfred Ngwa, Sébastien Penninckx, François Lux, Konstantin V Sokolov, Sharif M Ridwan, Jan Schuemann, H L Byrne, Alexander F. Bagley, Sunil Krishnan, James F. Hainfeld, Srinivas Sridhar, Sijumon Kunjachan, Department of Radiation Oncology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], The University of Texas M.D. Anderson Cancer Center [Houston], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Dana-Farber Cancer Institute [Boston], Department of Physics and Astronomy [Victoria], University of Victoria [Canada] (UVIC), Centre for Cancer Research and Cell Biology, Queen's University [Belfast] (QUB), School of Physics [Sydney], The University of Sydney, NanoHybrids, Inc. [Austin], Signalisation, radiobiologie et cancer, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Nanoprobes, Inc, Namur Research Institute for Life Sciences (NARILIS), Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), NH TherAguix SA [Meylan], Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Far Eastern Federal University (FEFU), Aurorad, Inc [Houston], Physikalisch-Technische Bundesanstalt [Berlin] (PTB), University of Connecticut Health Center [Farmington], Boston University [Boston] (BU), Université de Sherbrooke (UdeS), Northeastern University [Boston], Rice University [Houston], Department of Biomedical Engineering, The University of Texas at Austin, University of Texas at Austin [Austin], Oregon Health and Science University [Portland] (OHSU), and Mayo Clinic [Jacksonville]

Subjects
theranostics, Computer science, medicine.medical_treatment, Metal nanoparticles, Nanotechnology, Theranostic Nanomedicine, Modelling, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, SDG 3 - Good Health and Well-being, Vaccine adjuvant, medicine, Theranostic Nanomedicine/methods, Nanoparticle imaging, Humans, [CHIM]Chemical Sciences, Hyperthermia, Radiology, Nuclear Medicine and imaging, metal nanoparticles, radiotherapy, [PHYS]Physics [physics], Radiological and Ultrasound Technology, Radiotherapy, Induced, Radiation dose, modeling, Hyperthermia, Induced, Theranostics, Therapeutic applications of nanoparticles, Radiation therapy, therapeutic applications of nanoparticles, Hyperthermia induced, 030220 oncology & carcinogenesis, Drug delivery, Metal Nanoparticles/therapeutic use, immunotherapy, Immunotherapy, nanoparticle imaging
Abstract

International audience; This roadmap outlines the potential roles of metallic nanoparticles (MNPs) in the field of radiation therapy. MNPs made up of a wide range of materials (from Titanium, Z = 22, to Bismuth, Z = 83) and a similarly wide spectrum of potential clinical applications, including diagnostic, therapeutic (radiation dose enhancers, hyperthermia inducers, drug delivery vehicles, vaccine adjuvants, photosensitizers, enhancers of immunotherapy) and theranostic (combining both diagnostic and therapeutic), are being fabricated and evaluated. This roadmap covers contributions from experts in these topics summarizing their view of the current status and challenges, as well as expected advancements in technology to address these challenges.

Published
2020

26. Tumor-targeted pH-low insertion peptide delivery of theranostic gadolinium nanoparticles for image-guided nanoparticle-enhanced radiation therapy

Author

Maxime Parent, Fahmeed Hyder, Donald M. Engelman, Denise C. Hegan, Wu Liu, Qin Li, John C. Deacon, Peter M. Glazer, Bo Sun, Ravinder Nath, Kenneth B. Roberts, Olivier Tillement, Huagang Yan, Daniel Coman, Yanfeng Liu, Department of Therapeutic Radiology, Yale University [New Haven], Department of Radiation Oncology [Stanford], Stanford Medicine, Stanford University-Stanford University, Department of Molecular Biophysics and Biochemistry, Capital University of Medical Sciences [Beijing] (CUMS), Dalian Medical University [Dalian, Liaoning Province, China], Yale University School of Medicine, Department of Biomedical Engineering [Yale University], Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Original article, Cancer Research, Biodistribution, Gd, gadolinium, medicine.medical_treatment, Gadolinium, GdNP, gadolinium nanoparticle, Cell, chemistry.chemical_element, Enhanced permeability and retention effect, ICP-MS, inductively coupled plasma mass spectrometry, lcsh:RC254-282, Metallic nanoparticle radiosensitization, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, PBS, phosphate buffered saline, In vivo, NP, nanoparticle, pHLIP, pH-Low Insertion Peptide, medicine, [CHIM]Chemical Sciences, Radiosensitivity, EPR, enhanced permeability and retention, [PHYS]Physics [physics], Chemistry, Targeting acidic tumor microenvironment, RT, radiation therapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cell internalization, DCE, dynamic contrast-enhanced, Radiation physics, In vitro, 3. Good health, Radiation therapy, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, MRI
Abstract

International audience; Tumor targeting studies using metallic nanoparticles (NPs) have shown that the enhanced permeability and retention effect may not be sufficient to deliver the amount of intratumoral and intracellular NPs needed for effective in vivo radiosensitization. This work describes a pH-Low Insertion Peptide (pHLIP) targeted theranostic agent to enable image-guided NP-enhanced radiotherapy using a clinically feasible amount of injected NPs. Conventional gadolinium (Gd) NPs were conjugated to pHLIPs and evaluated in vitro for radiosensitivity and in vivo for mouse MRI. Cultured A549 human lung cancer cells were incubated with 0.5 mM of pHLIP-GdNP or conventional GdNP. Mass spectrometry showed 78-fold more cellular Gd uptake with pHLIP-GdNPs, and clonogenic survival assays showed 44% more enhanced radiosensitivity by 5 Gy irradiation with pHLIP-GdNPs at pH 6.2. In contrast to conventional GdNPs, MR imaging of tumor-bearing mice showed pHLIP-GdNPs had a long retention time in the tumor (>9 h), suitable for radiotherapy, and penetrated into the poorly-vascularized tumor core. The Gd-enhanced tumor corresponded with low-pH areas also independently measured by an in vivo molecular MRI technique. pHLIPs actively target cell surface acidity from tumor cell metabolism and deliver GdNPs into cells in solid tumors. Intracellular delivery enhances the effect of short-range radiosensitizing photoelectrons and Auger electrons. Because acidity is a general hallmark of tumor cells, the delivery is more general than antibody targeting. Imaging the in vivo NP biodistribution and more acidic (often more aggressive) tumors has the potential for quantitative radiotherapy treatment planning and pre-selecting patients who will likely benefit more from NP radiation enhancement.

Published
2020

27. Imaging and Characterization of Sustained Gadolinium Nanoparticle Release from Next Generation Radiotherapy Biomaterial

Author

Romy Mueller, Wilfred Ngwa, Michele Moreau, Olivier Tillement, Sayeda Yasmin-Karim, Jürgen Hesser, Ross Berbeco, Andrea Protti, Heidelberg University, Brigham and Women's Hospital [Boston], Dana-Farber Cancer Institute [Boston], Department of Radiation Oncology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Department of Physics and Applied Physics [Lowell], University of Massachusetts [Lowell] (UMass Lowell), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), Lurie Family Imaging Center, Dana-Farber Cancer Institute and Harvard Medical School, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Interdisciplinary Center for Scientific Computing (IWR), and Universität Heidelberg [Heidelberg]

Subjects
Materials science, General Chemical Engineering, Gadolinium, quantitative magnetic resonance imaging, chemistry.chemical_element, Nanoparticle, Article, 030218 nuclear medicine & medical imaging, lcsh:Chemistry, 03 medical and health sciences, chemistry.chemical_compound, [SPI]Engineering Sciences [physics], 0302 clinical medicine, In vivo, medicine, [CHIM]Chemical Sciences, magnetic resonance imaging, General Materials Science, Detection limit, [PHYS]Physics [physics], medicine.diagnostic_test, Biomaterial, Magnetic resonance imaging, gadolinium-based nanoparticles, 3. Good health, PLGA, chemistry, lcsh:QD1-999, 030220 oncology & carcinogenesis, Fiducial marker, Biomedical engineering, biomaterials
Abstract

Smart radiotherapy biomaterials (SRBs) present a new opportunity to enhance image-guided radiotherapy while replacing routinely used inert radiotherapy biomaterials like fiducials. In this study the potential of SRBs loaded with gadolinium-based nanoparticles (GdNPs) is investigated for magnetic resonance imaging (MRI) contrast. GdNP release from SRB is quantified and modelled for accurate prediction. SRBs were manufactured similar to fiducials, with a cylindrical shell consisting of poly(lactic-co-glycolic) acid (PLGA) and a core loaded with GdNPs. Magnetic resonance imaging (MRI) contrast was investigated at 7T in vitro (in agar) and in vivo in subcutaneous tumors grown with the LLC1 lung cancer cell line in C57/BL6 mice. GdNPs were quantified in-phantom and in tumor and their release was modelled by the Weibull distribution. Gd concentration was linearly fitted to the R1 relaxation rate with a detection limit of 0.004 mmol/L and high confidence level (R2 = 0.9843). GdNP loaded SRBs in tumor were clearly visible up to at least 14 days post-implantation. Signal decrease during this time showed GdNP release in vivo, which was calculated as 3.86 &plusmn, 0.34 &micro, g GdNPs release into the tumor. This study demonstrates potential and feasibility for SRBs with MRI-contrast, and sensitive GdNP quantification and release from SRBs in a preclinical animal model. The feasibility of monitoring nanoparticle (NP) concentration during treatment, allowing dynamic quantitative treatment planning, is also discussed.

Published
2020

28. Thermally induced evolution of the structure and optical properties of silicon nanowires

Author

Dana Yermukhamed, Vladimir Lysenko, Victor Yu. Timoshenko, Vladimir Sivakov, G.K. Mussabek, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Al-Farabi Kazakh National University, The National Research Nuclear University MEPhI (Moscow Engineering Physics Institute) [Moscow, Russia], Institute of Information and Computational Technologies (IICT), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Leibniz Institute of Photonic Technology (IPHT), Leibniz Association, Lomonosov Moscow State University (MSU), P. N. Lebedev Physical Institute of the Russian Academy of Sciences [Moscow] (LPI RAS), and Russian Academy of Sciences [Moscow] (RAS)

Subjects
Ostwald ripening, Silicon, Materials science, Nanowire, General Physics and Astronomy, chemistry.chemical_element, 02 engineering and technology, 7. Clean energy, 01 natural sciences, symbols.namesake, [SPI]Engineering Sciences [physics], 0103 physical sciences, [CHIM]Chemical Sciences, Crystalline silicon, 010302 applied physics, [PHYS]Physics [physics], Range (particle radiation), Total internal reflection, business.industry, Metal assisted etching, Nanowires, Thermal annealing, 021001 nanoscience & nanotechnology, Isotropic etching, lcsh:QC1-999, chemistry, symbols, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], Optoelectronics, Photonics, 0210 nano-technology, business, lcsh:Physics
Abstract

International audience; In the present paper, we report on the investigation of thermal annealing (TA) effect on structural and optical properties of crystalline silicon nanowires produced by metal-assisted chemical etching approach. In particular, the impact of TA on nanowire length, relative volume and size distribution of voids is described in terms of Lifshitz-Slyozov-Wagner theory considering the TA induced Oswald ripening in the SiNW arrays. It was also found that TA leads to a decrease of the SiNWs total reflection in the wide UV-VIS-IR spectral range. The reported effects can be used for tuning of crystalline SiNWs arrays in view of their further applications in photonics related fields.

Published
2020

29. Targeting brain metastases with ultrasmall theranostic nanoparticles, a first-in-human trial from an MRI perspective

Author

Olivier Tillement, Emmanuel L. Barbier, François Lux, Camille Verry, Jacques Balosso, Yannick Crémillieux, Sandrine Dufort, Irène Troprès, Sylvie Grand, Géraldine Le Duc, J. Pietras, Benoit Larrat, Sébastien Mériaux, Benjamin Lemasson, Centre Hospitalier Universitaire [Grenoble] (CHU), NH TherAguix SA [Meylan], NeuroImagerie Fonctionnelle et Perfusion Cérébrale, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), IRMaGe (IRMaGe), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), This work was performed on the IRMaGe platform member of France Life Imaging network (grant ANR-11-INBS-0006), ANR-11-INBS-0006,FLI,France Life Imaging(2011), ANR-19-P3IA-0003,MIAI,MIAI @ Grenoble Alpes(2019), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), VIDAL, Armelle, Infrastructures - France Life Imaging - - FLI2011 - ANR-11-INBS-0006 - INBS - VALID, MIAI @ Grenoble Alpes - - MIAI2019 - ANR-19-P3IA-0003 - P3IA - VALID, Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
medicine.medical_specialty, [SPI] Engineering Sciences [physics], Theranostic nanoparticles, medicine.medical_treatment, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, Phases of clinical research, 02 engineering and technology, [PHYS] Physics [physics], 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, [CHIM] Chemical Sciences, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, [CHIM]Chemical Sciences, Health and Medicine, Research Articles, ComputingMilieux_MISCELLANEOUS, [PHYS]Physics [physics], Multidisciplinary, business.industry, Melanoma, SciAdv r-articles, First in human, 021001 nanoscience & nanotechnology, medicine.disease, Image contrast, 3. Good health, Radiation therapy, 030220 oncology & carcinogenesis, Radiology, 0210 nano-technology, business, Mri findings, Research Article
Abstract

Intravenously injected theranostic Gd-based nanoparticles enable targeting and MRI detection of brain metastases in patients., The use of radiosensitizing nanoparticles with both imaging and therapeutic properties on the same nano-object is regarded as a major and promising approach to improve the effectiveness of radiotherapy. Here, we report the MRI findings of a phase 1 clinical trial with a single intravenous administration of Gd-based AGuIX nanoparticles, conducted in 15 patients with four types of brain metastases (melanoma, lung, colon, and breast). The nanoparticles were found to accumulate and to increase image contrast in all types of brain metastases with MRI enhancements equivalent to that of a clinically used contrast agent. The presence of nanoparticles in metastases was monitored and quantified with MRI and was noticed up to 1 week after their administration. To take advantage of the radiosensitizing property of the nanoparticles, patients underwent radiotherapy sessions following their administration. This protocol has been extended to a multicentric phase 2 clinical trial including 100 patients.

Published
2020

30. Thermal properties study of silicon nanostructures by photoacoustic techniques

Author

Fabrice Lemoine, Guillaume Castanet, Konstantinos Termentzidis, Vladimir Lysenko, Mykola Isaiev, K. Dubyk, Tetyana Nychyporuk, David Lacroix, Taras Shevchenko National University of Kyiv, Institut des Nanotechnologies de Lyon (INL), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre d'Energétique et de Thermique de Lyon (CETHIL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Laboratoire d'Energétique et de Mécanique Théorique Appliquée (LEMTA ), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), INL - Photovoltaïque (INL - PV), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-École Centrale de Lyon (ECL), Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Laboratoire Énergies et Mécanique Théorique et Appliquée (LEMTA ), 'Features of photothermal and photoacoustic processes in low-dimensional silicon-based semiconductor systems' (Ministry of Education and Science of Ukraine, State Registration Number 0118U000242), project HotLine (Agence nationale de la recherche, France, project number ANR-19-CE09-0003)., CNRS Energy unit (PEPS Cellule ENERGIE 2019) through the project Im-HESurNaASA, Scientific pole EMPP of University of Lorraine., ANR-19-CE09-0003,HotLiNe,Transport de chaleur aux interfaces et configurations nanometriques liquide/solide(2019), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École supérieure de Chimie Physique Electronique de Lyon (CPE)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
Thin films, Transducers, Nanowire, General Physics and Astronomy, FOS: Physical sciences, 02 engineering and technology, Applied Physics (physics.app-ph), Heat sink, Porous silicon, 01 natural sciences, Heat capacity, [SPI.MAT]Engineering Sciences [physics]/Materials, Thermodynamic properties, Thermal conductivity, Semiconductor nanostructures, 0103 physical sciences, Thermal, Mesoscale and Nanoscale Physics (cond-mat.mes-hall), Composite material, [PHYS.COND]Physics [physics]/Condensed Matter [cond-mat], Porosity, 010302 applied physics, Physics, [SPI.ACOU]Engineering Sciences [physics]/Acoustics [physics.class-ph], Condensed Matter - Materials Science, Condensed Matter - Mesoscale and Nanoscale Physics, Nanowires, thermal properties, Materials Science (cond-mat.mtrl-sci), Physics - Applied Physics, Computer simulation, 021001 nanoscience & nanotechnology, silicon nanowires arrays, porous silicon, Etching, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], [SPI.MECA.THER]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Thermics [physics.class-ph], Photoacoustic Techniques, 0210 nano-technology, Materials properties, Scanning electron microscopy, piezoelectric detection, photoacoustic effect
Abstract

International audience; The photoacoustic method with piezoelectric detection for the simultaneous evaluation of the thermophysical properties is proposed. The approach is based on the settling of an additional heat sink for redistribution of heat fluxes deposited on the sample surface. Firstly, the approach was tested on the porous silicon with welldefined morphology and well-studied properties. Then, heat capacity and thermal conductivity of silicon nanowires arrays have been investigated by recovering the experimental data through numerical simulations. The decrease of heat capacity and effective thermal conductivity of the samples upon increasing thickness and porosity of the sample is observed. Such behavior could be caused by the increase of the structure heterogeneity. In particular, this can be related to larger disorder (increased density of broken nanowires and larger porosity) that appears during the etching process of the thick layers.

Published
2020

31. Nebulised Gadolinium-Based Nanoparticles for a Multimodal Approach: Quantitative and Qualitative Lung Distribution Using Magnetic Resonance and Scintigraphy Imaging in Isolated Ventilated Porcine Lungs

Author

Bei Zhang, Anthony Clotagatide, Yoann Montigaud, Sophie Perinel, Olivier Tillement, Lara Leclerc, Clémence Bal, François Lux, Nathalie Prevot, Nobuyasu Ichinose, Yannick Crémillieux, Jérémie Pourchez, Noël Pinaud, INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Etienne, Université de Bordeaux (UB), Canon Medical Systems Corporation, Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), and Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Swine, aerosol, [SDV]Life Sciences [q-bio], Gadolinium, theranostic, Pharmaceutical Science, Nanoparticle, Contrast Media, Metal Nanoparticles, 02 engineering and technology, Scintigraphy, 01 natural sciences, environment and public health, [SPI]Engineering Sciences [physics], International Journal of Nanomedicine, Drug Discovery, Precision Medicine, Lung, ComputingMilieux_MISCELLANEOUS, Original Research, [PHYS]Physics [physics], medicine.diagnostic_test, Multimodal therapy, General Medicine, 021001 nanoscience & nanotechnology, Magnetic Resonance Imaging, 3. Good health, medicine.anatomical_structure, 0210 nano-technology, ex vivo model, MRI, MRI contrast agent, Biophysics, pulmonary delivery, chemistry.chemical_element, Bioengineering, 010402 general chemistry, Biomaterials, Meglumine, Organ Culture Techniques, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Organometallic Compounds, Distribution (pharmacology), [CHIM]Chemical Sciences, Animals, Humans, Radionuclide Imaging, Aerosols, Nebulizers and Vaporizers, Organic Chemistry, Magnetic resonance imaging, SPECT/CT, Respiration, Artificial, 0104 chemical sciences, chemistry, Biomedical engineering
Abstract

Yoann Montigaud,1 Jérémie Pourchez,1 Lara Leclerc,1 Olivier Tillement,2 Anthony Clotagatide,3,4 Clémence Bal,5 Noël Pinaud,5 Nobuyasu Ichinose,6 Bei Zhang,7 Sophie Perinel,3,4 François Lux,2,8 Yannick Crémillieux,5 Nathalie Prevot3,4 1Mines Saint-Etienne, Univ Lyon, Univ Jean Monnet, INSERM, U 1059 Sainbiose, Centre CIS, Saint-Etienne, France; 2Institut Lumière Matière, Université de Lyon, Villeurbanne, France; 3INSERM U 1059 Sainbiose, Université Jean Monnet, Saint-Etienne, France; 4CHU Saint-Etienne, Saint-Etienne, France; 5IBIO, Bordeaux, France; 6Canon Medical Systems Corporation, Otawara, Japan; 7Canon Medical Systems Europe, Zoetermeer, Netherlands; 8Institut Universitaire de France (IUF), Paris, FranceCorrespondence: Jérémie PourchezMines Saint-Etienne, 158 Cours Fauriel, CS 62362, Saint-Etienne, Cedex 2 42023, FranceTel +33 4 77 42 01 80Email pourchez@emse.frPurpose: This study aims at determining lung distribution of gadolinium-based polysiloxane nanoparticles, AGuIX® (small rigid platform – SRP), as a potential theranostic approach by the pulmonary route.Methods: First, the aerodynamic size distribution and the aerosol output rate were thoroughly characterized. Then, a multimodal approach using magnetic resonance (MR) and gamma-camera (GC) imaging allows to assess the deposition of the aerosolised nanoparticles in the respiratory tract using isolated ventilated porcine lungs.Results: The SRP has proven to be radiolabelled by radioisotope with a good yield. Crude SRP or radiolabelled ones showed the same aerodynamic size distribution and output as a conventional molecular tracer, as sodium fluoride. With MR and GC imaging approaches, the nebulised dose represented about 50% of the initial dose of nanoparticles placed in the nebuliser. Results expressed as proportions of the deposited aerosol showed approximately a regional aerosol deposition of 50% of the deposited dose in the lungs and 50% in the upper airways. Each technique assessed a homogeneous pattern of deposited nanoparticles in Lungs. MR observed a strong signal enhancement with the SRP, similar to the one obtained with a commonly used MRI contrast agent, gadoterate meglumine.Conclusion: As a known theranostic approach by intravenous administration, SRP appeared to be easily aerosolised with a conventional nebuliser. The present work proves that pulmonary administration of SRP is feasible in a human-like model and allows multimodal imaging with MR and GC imaging. This work presents the proof of concept of SRP nebulisation and aims to generate preclinical data for the potential clinical transfer of SRP for pulmonary delivery.Keywords: aerosol, pulmonary delivery, ex vivo model, MRI, SPECT/CT, theranostic

Published
2020

32. Anti-MUC1-C Antibody-Conjugated Nanoparticles Potentiate the Efficacy of Fractionated Radiation Therapy

Author

Peter P. Ghoroghchian, Alexandre Detappe, Caining Jin, Marie-Charlotte Diringer, Clelia Mathieu, Vu-Long Tran, Michael P. Agius, Donald Kufe, Olivier Tillement, Xavier Pivot, François Lux, Dana-Farber Cancer Institute [Boston], Centre Paul Strauss, CRLCC Paul Strauss, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Strasbourg Europe (ICANS), Institut Universitaire de France (IUF), and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)

Subjects
Cancer Research, Immunoconjugates, Lung Neoplasms, medicine.medical_treatment, Gadolinium, chemistry.chemical_element, Mice, Nude, Triple Negative Breast Neoplasms, Pharmacology, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, [SPI]Engineering Sciences [physics], Mice, 0302 clinical medicine, Pharmacokinetics, In vivo, Cell Line, Tumor, medicine, Tumor Microenvironment, [CHIM]Chemical Sciences, Animals, Humans, Immunologic Factors, Radiology, Nuclear Medicine and imaging, MUC1, ComputingMilieux_MISCELLANEOUS, [PHYS]Physics [physics], Tumor microenvironment, Mice, Inbred BALB C, Radiation, business.industry, Mucin-1, Washout, Antibodies, Monoclonal, 3. Good health, Radiation therapy, Oncology, chemistry, 030220 oncology & carcinogenesis, Nanoparticles, Female, Dose Fractionation, Radiation, business, Conjugate, DNA Damage
Abstract

PURPOSE: Heavy-metal chelators and inorganic nanoparticles (NPs) have been examined as potential radioenhancers to increase the efficacy of external beam radiation therapy for various cancers. Most of these agents have, unfortunately, displayed relatively poor pharmacokinetic properties, which limit the percentage of injected dose (%ID/g) that localizes to tumors and which shorten the window for effective radiation enhancement due to rapid tumor washout. METHODS AND MATERIALS: To address these challenges, we sought to conjugate gadolinium-based ultrasmall (

Published
2020

33. Radiobiological Implications of Nanoparticles Following Radiation Treatment

Author

Miriam A. Barry, Giuseppe Schettino, Olivier Tillement, K Ricketts, Gary Royle, R Ahmad, Ben Russell, Quentin A. Pankhurst, Division of Surgery and Interventional Science [London, UK], University College of London [London] (UCL), National Physical Laboratory [Teddington] (NPL), University of Surrey (UNIS), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
Cancer therapy, Gadolinium, Cell, Iron oxide, chemistry.chemical_element, Nanoparticle, 02 engineering and technology, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Naoparticle‐enhanced radiotherapy, Ionizing radiation, chemistry.chemical_compound, [SPI]Engineering Sciences [physics], 020401 chemical engineering, medicine, [CHIM]Chemical Sciences, General Materials Science, Irradiation, 0204 chemical engineering, Clonogenic assay, Radiosensitization, [PHYS]Physics [physics], Full Paper, Radiochemistry, General Chemistry, Full Papers, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 3. Good health, Radiation therapy, medicine.anatomical_structure, chemistry, Colloidal gold, nanoparticle‐enhanced radiotherapy, 0210 nano-technology
Abstract

Materials with a high atomic number (Z) are shown to cause an increase in the level of cell kill by ionizing radiation when introduced into tumor cells. This study uses in vitro experiments to investigate the differences in radiosensitization between two cell lines (MCF‐7 and U87) and three commercially available nanoparticles (gold, gadolinium, and iron oxide) irradiated by 6 MV X‐rays. To assess cell survival, clonogenic assays are carried out for all variables considered, with a concentration of 0.5 mg mL−1 for each nanoparticle material used. This study demonstrates differences in cell survival between nanoparticles and cell line. U87 shows the greatest enhancement with gadolinium nanoparticles (2.02 ± 0.36), whereas MCF‐7 cells have higher enhancement with gold nanoparticles (1.74 ± 0.08). Mass spectrometry, however, shows highest elemental uptake with iron oxide and U87 cells with 4.95 ± 0.82 pg of iron oxide per cell. A complex relationship between cellular elemental uptake is demonstrated, highlighting an inverse correlation with the enhancement, but a positive relation with DNA damage when comparing the same nanoparticle between the two cell lines., This study investigates the enhancement effect of nanoparticles combined with radiotherapy, relating both cell survival and DNA damage to cellular elemental uptake. Different nanoparticles and cancer cells are used, where in all cases, nanoparticles cause a level of enhancement. The complexity in enhancement with increasing uptake can be seen, highlighting different mechanisms contributing to the enhancement effect.

Published
2020

34. Gadolinium-based nanoparticles can overcome the radioresistance of head and neck squamous cell carcinoma through the induction of autophagy

Author

S. Gerbaud, Stéphanie Simonet, Dominique Ardail, O. Tillement, C. Malesys, David Béal, Walid Rachidi, F. Lux, Hussein Fayyad-Kazan, Claire Rodriguez-Lafrasse, Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Unité Médicale d'Oncologie Moléculaire et Transfert (UMOMT), Hospices Civils de Lyon (HCL), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Biomicrotechnologie et génomique fonctionnelle (BIOMICS ), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Laboratory of Cancer Biology and Molecular Immunology, ANR-11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation(2011), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Genetics and Chemogenomics (GenChem), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)

Subjects
Programmed cell death, DNA damage, medicine.medical_treatment, 0206 medical engineering, Cell, Biomedical Engineering, Pharmaceutical Science, Medicine (miscellaneous), Metal Nanoparticles, Bioengineering, Apoptosis, Gadolinium, 02 engineering and technology, Cell Line, [SPI]Engineering Sciences [physics], Radioresistance, Cell Line, Tumor, medicine, Autophagy, Humans, [CHIM]Chemical Sciences, General Materials Science, [PHYS]Physics [physics], Tumor, business.industry, Squamous Cell Carcinoma of Head and Neck, Carcinoma, 021001 nanoscience & nanotechnology, medicine.disease, 020601 biomedical engineering, Head and neck squamous-cell carcinoma, 3. Good health, Radiation therapy, medicine.anatomical_structure, Squamous Cell, Head and Neck Neoplasms, Cancer research, Carcinoma, Squamous Cell, 0210 nano-technology, business
Abstract

Radiation therapy is a mainstay in the therapeutic management of Head and Neck Squamous Cell Carcinoma (HNSCC). Despite significant progress in this field, radioresistance still accounts for most treatment failures. Gadolinium-based nanoparticles (GBNs) have shown great promises as radiosensitizers but the underlying sensitizing mechanism is still largely unknown with regards to the disparities obtained in in vitro studies. In this study, we show that a new formulation of GBNs, AGuIX®, can radiosensitize HNSCC after cell uptake and further accumulation in lysosomes. Although radiation alone triggered late apoptosis and mitochondrial impairment, the pre-treatment with GBNs led to complex DNA damage and a specific increase of autophagic cell death. In addition, a significant radio-enhancement effect was obtained after the pre-conditioning of cells with a glutathione inhibitor before GBNs treatment and radiation exposure. Overall, our results provide additional information on the radio-enhancing properties of GBNs in the management of radioresistant HNSCC.

Published
2020

35. Some Types of Carbon-based Nanomaterials as Contrast Agents for Photoacoustic Tomography

Author

Mykola Isaiev, Aleksey Rozhin, Olga Levinson, Boris Zousman, Volodymyrska St., Kyiv, Ukraine, K. Dubyk, Lesia Chepela, Vladimir Lysenko, Sergei Alekseev, A. G. Kuzmich, Alain Géloën, Taras Shevchenko National University of Kyiv, Ray Techniques Ltd., Aston University [Birmingham], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire Énergies et Mécanique Théorique et Appliquée (LEMTA ), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut des Nanotechnologies de Lyon (INL), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-École Centrale de Lyon (ECL), Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), and ISAIEV, Mykola

Subjects
Materials science, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, фотоакустична томографія, Nanotechnology, photoacoustic tomography, [SPI.MAT]Engineering Sciences [physics]/Materials, 3D-зображення, Carbon based nanomaterials, 3D imaging, фантоми тканин, tissue phantoms, General Materials Science, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, Carbon nanomaterials, carbon nanomaterials, Radiation, Photoacoustic tomography, Photoacoustic tomography PACS numbers: 81.05.Uw, вуглецеві наноматеріали, Contrast (music), Tissue phantoms, Condensed Matter Physics, [PHYS.COND.CM-SCM] Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft], [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, 42.30.Wb, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft]
Abstract

Ця стаття присвячена вивченню різних наноматеріалів на основі вуглецю як фотоакустичних контрастних речовин. Дослідницька робота проводилася на фантомі тканини на основі агарози, що містить включення з карбоновими наноматеріалами та без них. Включення було створено з більш високою густиною порівняно з фантомом з метою імітування пухлини. Для вимірювання рівня фотоакустичного сигналу та його підсилення, спричиненого наявністю нановключень, було використано спеціально розроблений фотоакустичний зонд. Зонд складається з буфера для часового розділення сигналу, що надходить від джерела збудження, п'єзоелектричного перетворювача та підсилювача. Точкові вимірювання сигналу проводилися для отримання двовимірної карти величини фотоакустичного сигналу та фазової затримки реєстрації сигналу. На основі затримки фази реконструювали фотоакустичні 3D зображення шляхом оцінки координати глибини на основі швидкості звуку в тканині. Як джерело збудження було використано світлове випромінювання від Nd:YAG лазера з тривалістю імпульсу 16 нс та довжиною хвилі 1064 нм. По-перше, ми розглядали тканинний фантом із пухлиною, покритою оксидом графена (GO) в якості контрольного. Показано, що використання GO призводить до значного поліпшення контрасту зображення. Далі систематично вивчалися пухлини, покриті нанодіамантами (NDs) та наночастинками фтороксиду вуглецю (CFO). Амплітуда фотоакустичних сигналів, зареєстрованих від таких фантомів пухлини, на порядок менша, ніж сигнал, одержуваний від GO. Всі три типи досліджуваних наноматеріалів на основі вуглецю (GO, NDs, CFO) дають стабільний фотоакустичний сигнал, що дозволяє вважати їх хорошими кандидатами для подальших експериментів in vitro у фотоакустичній візуалізації для біологічних застосувань. Залежності рівня сигналу від концентрації наночастинок вимірювали для окремих типів наночастинок. Враховуючи набагато ефективніше проникнення NDs та CFO наночастинок всередину клітин, а також їх надзвичайно низьку цитотоксичність, ці обидва типи вуглецевих наноматеріалів можуть бути використані для подальших експериментів in vivo. This paper is devoted to the study of various carbon-based nanomaterials as photoacoustic contrast agents. The research work was performed on agarose-based tissue phantom containing inclusions with and without carbon-based nanomaterials. The inclusion was created with the higher density compared to phantom in order to simulate a tumor. A specially designed photoacoustic probe was introduced for measuring a level of photoacoustic signal and its enhancement caused by the nanoinclusions presence. The probe consists of a buffer for time separation of the signal coming from the excitation source, piezoelectric transducer, and amplifier. A point-by-point measurement of the signal was performed to obtain a two-dimensional map from magnitude of photoacoustic signal and phase delay of the signal registration. From phase delay the 3D photoacoustic images were reconstructed by evaluation of the depth coordinate based on the tissue sound velocity. As an excitation source the light radiation from Nd:YAG laser with a 16 ns pulse duration and a 1064 nm wavelength was used. Firstly, we considered tissue phantom with a tumor covered by graphene oxide as a reference one. It has been shown that the use of graphene oxide leads to significant improvement of the image contrast. Further, the tumors labelled with nanodiamonds (NDs) and carbon fluoroxide (CFO) nanoparticles (NPs) were studied systematically. Amplitude of the photoacoustic signals registered from such tumor phantoms are one order of magnitude lower than the signal ensured by graphene oxide. All three types of the studied carbon-based nanomaterials (GO, NDs, CFO) give stable photoacoustic signal, this allows to consider them as good candidates for further in-vitro experiments in photoacoustic imaging for biological applications. The dependences of the signal level as a function of the NPs concentration were measured for types of NPs. Considering much more efficient penetration of NDs and CFO NPs inside the cells as well as their extremely low cytotoxicity, these both types of carbon nanomaterials could be used for further in-vivo experiments.

Published
2020

36. EPR-mediated tumor targeting using ultrasmall-hybrid nanoparticles: From animal to human with theranostic AGuIX nanoparticles

Author

Bort, guillaume, Lux, François, Dufort, Sandrine, Crémillieux, Yannick, Verry, Camille, Tillement, Olivier, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, NH TherAguix SA [Meylan], Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de radiothérapie- CHU de Grenoble, CHU Grenoble, Synchrotron Radiation for Biomedical Research Inserm UA7, Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Bort, Guillaume, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[CHIM.INOR] Chemical Sciences/Inorganic chemistry, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Siloxanes, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, theranostic, [SDV]Life Sciences [q-bio], Gadolinium, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, Theranostic Nanomedicine, clinical translation, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, ultrasmall nanoparticle, Neoplasms, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Animals, Humans, Tissue Distribution, Particle Size, ComputingMilieux_MISCELLANEOUS, Chelating Agents, EPR effect, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV] Life Sciences [q-bio], [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, AGuIX, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Nanoparticles
Abstract

International audience; Interest of tumor targeting through EPR effect is still controversial due to intrinsic low targeting efficacy and rare translation to human cancers. Moreover, due to different reasons, it has generally been described for relatively large nanoparticles (NPs) (hydrodynamic diameter > 10 nm). In this review EPR effect will be discussed for ultrasmall NPs using the example of the AGuIX® NP (Activation and Guiding of Irradiation by X-ray) recently translated in clinic. AGuIX® NP is a 4 ± 2 nm hydrodynamic diameter polysiloxane based NP. Since AGuIX® NP biodistribution is monitored by magnetic resonance imaging (MRI) and its activation is triggered by irradiation upon X-rays, this NP is well adapted for a theranostic approach of radiotherapy cancer treatment. Here we show that AGuIX® NP is particularly well suited to benefit from EPR-mediated tumor targeting thanks to an ultrasmall size and efficacy under irradiation at small dose. Indeed, intravenously-injected AGuIX® NP into rodent cancer models passively reached the tumor and revealed no toxicity, favoured by renal clearance. Moreover, translation of AGuIX® NP accumulation and retention into humans carrying brain metastases was validated during a first-in-man phase Ib trial taking advantage of easy biodistribution monitoring by MRI.

Published
2020

37. Feasibility of intratumoral 165Holmium siloxane delivery to induced U87 glioblastoma in a large animal model, the Yucatan minipig

Author

Cédric Louis, Lionel Marcon, Mehrdad Khoshnevis, Catherine Bonnefont-Rebeix, Frédérique Ponce, Thierry Buronfosse, T. Roger, Claude Carozzo, Richard Brown, Manuel Bardiès, Olivier Tillement, Hélène Gehan, Christophe Nennig, Sara Belluco, Ilyes Zahi, Bodescot, Myriam, Interactions Cellules Environnement - UR (ICE), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), EVEON [Montbonnot-Saint-Martin], Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Nano-H SAS [Saint-Quentin Fallavier], Advanced Accelerator Applications [Saint-Genis-Pouilly], Department of Endocrinology [Marcy-l'Étoile], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Rongeurs Sauvages, Risques Sanitaires et Gestion des Populations - UR 1233 (RS2GP), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Clinical Oncology Unit [Marcy-l'Étoile], This work was supported by the BPifrance [ISI 2013–2018]., and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Swine, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Amperometry, Diagnostic Radiology, Holmium, 0302 clinical medicine, Medicine and Health Sciences, Malignant tumors, U87, Tomography, Cancers and neoplasms, Mammals, Multidisciplinary, Organic Compounds, Brain Neoplasms, Radiology and Imaging, Standard treatment, Eukaryota, 3. Good health, Chemistry, Bioassays and Physiological Analysis, Renal cancer, Oncology, 030220 oncology & carcinogenesis, Cancer treatment, Vertebrates, Physical Sciences, Computed axial tomography, Swine, Miniature, Medicine, Female, Anatomy, Research Article, medicine.drug, Histology, Siloxanes, Imaging Techniques, Science, Transplantation, Heterologous, Brain tumor, Neuroimaging, Surgical and Invasive Medical Procedures, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Research and Analysis Methods, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Diagnostic Medicine, Cell Line, Tumor, medicine, Animals, Humans, Dosimetry, Bioelectrochemical Analysis, Tomography, Emission-Computed, Single-Photon, Chemotherapy, Temozolomide, business.industry, Organic Chemistry, Organisms, Chemical Compounds, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Biology and Life Sciences, medicine.disease, Radiation therapy, Transplantation, Disease Models, Animal, Amniotes, Feasibility Studies, Radiopharmaceuticals, Biochemical Analysis, Glioblastoma, business, Nuclear medicine, 030217 neurology & neurosurgery, Neuroscience
Abstract

International audience; Glioblastoma is the most aggressive primary brain tumor leading to death in most of patients. It comprises almost 50-55% of all gliomas with an incidence rate of 2-3 per 100,000. Despite its rarity, overall mortality of glioblastoma is comparable to the most frequent tumors. The current standard treatment combines surgical resection, radiotherapy and chemotherapy with temozolomide. In spite of this aggressive multimodality protocol, prognosis of glioblastoma is poor and the median survival remains about 12-14.5 months. In this regard, new therapeutic approaches should be developed to improve the life quality and survival time of the patient after the initial diagnosis. Before switching to clinical trials in humans, all innovative therapeutic methods must be studied first on a relevant animal model in preclinical settings. In this regard, we validated the feasibility of intratumoral delivery of a holmium (Ho) microparticle suspension to an induced U87 glioblastoma model. Among the different radioactive beta emitters, 166Ho emits high-energy β(-) radiation and low-energy γ radiation. β(-) radiation is an effective means for tumor destruction and γ rays are well suited for imaging (SPECT) and consequent dosimetry. In addition, the paramagnetic Ho nucleus is a good asset to perform MRI imaging. In this study, five minipigs, implanted with our glioblastoma model were used to test the injectability of 165Ho (stable) using a bespoke injector and needle. The suspension was produced in the form of Ho microparticles and injected inside the tumor by a technique known as microbrachytherapy using a stereotactic system. At the end of this trial, it was found that the 165Ho suspension can be injected successfully inside the tumor with absence or minimal traces of Ho reflux after the injections. This injection technique and the use of the 165Ho suspension needs to be further assessed with radioactive 166Ho in future studies.

Published
2020

38. Empirical and Theoretical Characterization of the Diffusion Process of Different Gadolinium-Based Nanoparticles within the Brain Tissue after Ultrasound-Induced Permeabilization of the Blood-Brain Barrier

Author

Conti, Allegra, Magnin, Remi, Gerstenmayer, Matthieu, Tsapis, Nicolas, Dumont, Erik, Tillement, Olivier, Lux, François, Le Bihan, Denis, Mériaux, Sébastien, Della Penna, Stefania, Larrat, Benoit, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Image Guided Therapy (IGT), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Department of Clinic Sciences and Bioimaging, University G. d'Annunzio Chieti-Pescara, European Project: 600382,EC:FP7:PEOPLE,FP7-PEOPLE-2012-COFUND,ENHANCED EUROTALENTS(2014), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut Galien Paris-Sud (IGPS), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
Male, lcsh:Medical technology, Article Subject, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Sulfur Hexafluoride, Contrast Media, Nanoconjugates, Capillary Permeability, Rats, Sprague-Dawley, Diffusion, [SPI]Engineering Sciences [physics], Meglumine, Heterocyclic Compounds, Organometallic Compounds, Animals, Particle Size, Phospholipids, Microbubbles, Phantoms, Imaging, Settore FIS/07, Corpus Striatum, Rats, lcsh:R855-855.5, Ultrasonic Waves, Blood-Brain Barrier, Extracellular Space, Algorithms, Research Article
Abstract

International audience; Low-intensity focused ultrasound (FUS), combined with microbubbles, is able to locally, and noninvasively, open the blood-brain barrier (BBB), allowing nanoparticles to enter the brain. We present here a study on the di usion process of gadolinium-based MRI contrast agents within the brain extracellular space after ultrasound-induced BBB permeabilization. ree compounds were tested (MultiHance, Gadovist, and Dotarem). We characterized their di usion through in vivo experimental tests supported by theoretical models. Speci cally, by estimation of the free di usion coe cients from in vitro studies and of apparent di usion coe cients from in vivo experiments, we have assessed tortuosity in the right striatum of 9 Sprague Dawley rats through a model correctly describing both vascular permeability as a function of time and di usion processes occurring in the brain tissue. is model takes into account acoustic pressure, particle size, blood pharmacokinetics, and di usion rates. Our model is able to fully predict the result of a FUS-induced BBB opening experiment at long space and time scales. Recovered values of tortuosity are in agreement with the literature and demonstrate that our improved model allows us to assess that the chosen permeabilization protocol preserves the integrity of the brain tissue.

Published
2019

39. Thermal conductivity of nanofluids formed by carbon flurooxide mesoparticles

Author

R. M. Burbelo, K. Dubyk, Mykola Isaiev, Sergei Alekseev, Vladimir Lysenko, Taras Shevchenko National University of Kyiv, Laboratoire Énergies et Mécanique Théorique et Appliquée (LEMTA ), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), INL - Spectroscopies et Nanomatériaux (INL - S&N), Institut des Nanotechnologies de Lyon (INL), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
Materials science, General Chemical Engineering, General Physics and Astronomy, Nanoparticle, chemistry.chemical_element, 02 engineering and technology, 01 natural sciences, [SPI.MAT]Engineering Sciences [physics]/Materials, Thermal conductivity, Nanofluid, 0103 physical sciences, Thermal, Molecule, General Materials Science, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, ComputingMilieux_MISCELLANEOUS, General Environmental Science, 010302 applied physics, Photoacoustic effect, General Engineering, 021001 nanoscience & nanotechnology, Chemical engineering, chemistry, Volume fraction, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], General Earth and Planetary Sciences, 0210 nano-technology, Carbon
Abstract

Mesoparticles with characteristic sizes larger than all known molecules and smaller than usual nanoparticles can easily penetrate inside living cells. Thus, they appear to be especially promising for cancer theranostic application. However, presence of mesoparticles can strongly perturb physico-chemical properties of the biological media in which they are incorporated, it is crucial to know a magnitude of such perturbations. For example, thermal properties of liquid solutions with dispersed mesoparticles are crucial for development of theranostic approaches based on photoacoustic effect. In this paper, thermal transport in nanofluids formed by carbon flurooxide (CFO) mesoparticles is reported. A significant non-linear enhancement of the thermal conductivity of the nanofluids (up to 85%, in comparison with initial basic liquids) depending on volume fraction of the dispersed CFO mesoparticles was found. It was revealed that the thermal conductivity rise can be explained by existence of interfacial layers between the mesoparticles and the hosting liquids.

Published
2019

40. Design of a robust and compact gamma sensor: Assessment of uranium detection in underground COx mudstone for nuclear waste management

Author

Marie-Geneviève Blanchin, Romain V.H. Dagnelie, Virginie Blin, Agnès Vinsot, Yanick Lettry, Benoit Hautefeuille, Zhenhua Lin, AXINT SAS, CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Agence Nationale pour la Gestion des Déchets Radioactifs (ANDRA), Solexperts AG, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
Physics, [PHYS]Physics [physics], Nuclear and High Energy Physics, Radionuclide, Nuclear engineering, Radioactive waste, chemistry.chemical_element, Context (language use), Actinide, Uranium, Natural uranium, 010502 geochemistry & geophysics, 010403 inorganic & nuclear chemistry, 01 natural sciences, 7. Clean energy, 0104 chemical sciences, [SPI]Engineering Sciences [physics], chemistry, Calibration, [CHIM]Chemical Sciences, Sensitivity (control systems), Instrumentation, 0105 earth and related environmental sciences
Abstract

International audience; In the context of deep geological radioactive waste disposal in France, various experiments have been designed, including in situ hydrogeological tests, chemical measurements and diffusion experiments. In this paper, we focus on in situ Diffusion of Radionuclides (DRN) tests, typically for actinide diffusion. These tests involved the construction of a powerful and qualified instrument that fulfills requirements for in situ radionuclides measurements. This implied a very specific design of four channels 1x1 inch cylinder YSO gamma-ray sensors, satisfying severe geometric and operational constraints while displaying high sensitivity and robust, real time on-line performance. The calibration of such sensors was assessed regarding their ability to quantify the minimum quantity of natural uranium that could be detected with and without the presence of Callovian–Oxfordian mudstone (COx) screens. Its design, calibration,and detection sensitivity are described in the present paper. The sensor sensitivity at 12 and 6 counts/second/g(U) without and with COx screening effect were determined for energy peak counting windows (50–105 keV) respectively. This was equivalent to a limit of detection (LOD) of uranium at 42.5 mg and 126 mg without and with a 7 cm thickness of COx sample. These sensors provided the first trial for in situ actinide diffusion tests in the context of nuclear waste management.

Published
2019

41. Ultrasmall theranostic gadolinium-based nanoparticles improve high-grade rat glioma survival

Author

Sandrine Dufort, Géraldine Le Duc, Steven D. Chang, Lucie Sancey, Camille Verry, Stéphane Roux, Olivier Tillement, François Lux, Elke Bräuer-Krisch, Emmanuel L. Barbier, Michael Zhang, Geoffrey Appelboom, NanoH-sas, Stanford University Medical Center, Service de radiothérapie- CHU de Grenoble, CHU Grenoble, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), European Synchrotron Radiation Facility (ESRF), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), ANR-19-P3IA-0003,MIAI,MIAI @ Grenoble Alpes(2019), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
Male, Radiation-Sensitizing Agents, Gadolinium, chemistry.chemical_element, Contrast Media, [SDV.CAN]Life Sciences [q-bio]/Cancer, Theranostic Nanomedicine, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Glioma, medicine, Temozolomide, Animals, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Radiosensitizers, business.industry, Brain Neoplasms, Contralateral hemisphere, Washout, General Medicine, Chemoradiotherapy, medicine.disease, Magnetic Resonance Imaging, Rats, Inbred F344, Rats, 9l glioma, Neurology, chemistry, Theranostic, Chemoradiation, 030220 oncology & carcinogenesis, Nanoparticles, Surgery, Radiotherapy treatment, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.IB]Life Sciences [q-bio]/Bioengineering, Neurology (clinical), business, Nuclear medicine, Glioblastoma, 030217 neurology & neurosurgery, Median survival, medicine.drug
Abstract

International audience; We formulated an ultra-small, gadolinium-based nanoparticle (AGuIX) with theranostic properties to simultaneously enhance MRI tumor delineation and radiosensitization in a glioma model. The 9L glioma cells were orthotopically implanted in 10-week-old Fischer rats. The intra-tumoral accumulation of AGuIX was quantified using MRI T1-maps. Rats randomized to intervention cohorts were subsequently treated with daily temozolomide for five consecutive days before radiotherapy treatment. Collectively, a series of 32 rats were divided into untreated (n = 7), temozolomide-only (n = 7), temozolomide and MRT (n = 9), AGuIX and MRT (n = 7), and triple therapy (temozolomide, AGuIX NPs, and MRT; n = 9) cohorts. AGuIX nanoparticles achieved a maximum intra-tumoral concentration (expressed as concentration of Gd3+) at 1 h after intravenous injection, reaching a mean of 227.9 ± 60 lM. This was compared to concentrations of 10.5 ± 9.2 lM and 62.9 ± 24.7 lM in the contralateral hemisphere and cheek, respectively. There was a slower washout in the intra-tumor region, with sustained tumor-to-contralateral ratio of AGuIX, up to 14-fold, for each time point. The combination of AGuIX or temozolomide with MRT improved the median survival time (40 days) compared to the MeST of control rats (25 days) (p < 0.002). There was a trend towards further increased survival when the three treatments were combined (MeST of 46 days). This study demonstrated the selective accumulation of AGuIX in high grade glioma, as well as the potential survival benefits when combined with chemoradiation.

Published
2019

42. Functionalization of theranostic AGuIX® nanoparticles for PET/MRI/optical imaging

Author

Alan Courteau, Mathieu Moreau, Vu-Long Tran, Vivek Thakare, Franck Denat, Eloise Thomas, François Lux, Olivier Tillement, Frédéric Boschetti, Anthony Romieu, Marco Natuzzi, Jean-Marc Vrigneaud, Bertrand Collin, Cédric Louis, Stéphane Roux, CheMatech - Macrocycle Design Technologies, Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Nano-H SAS [Saint-Quentin Fallavier], Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)

Subjects
Materials science, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, General Chemical Engineering, [SDV]Life Sciences [q-bio], Nanoparticle, Nanotechnology, [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, General Chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 3. Good health, 0104 chemical sciences, chemistry.chemical_compound, Optical imaging, Functionalized nanoparticles, chemistry, Michael reaction, Surface modification, [CHIM]Chemical Sciences, Chelation, Cyanine, 0210 nano-technology, [CHIM.RADIO]Chemical Sciences/Radiochemistry
Abstract

International audience; A novel trifunctional imaging probe containing a chelator of radiometal for PET, a NIR heptamethine cyanine dye, and a bioconjugatable handle, has been grafted onto AGuIX® nanoparticles via a Michael addition reaction. The resulting functionalized nanoparticles have been fully characterized, radiolabelled with 64Cu, and evaluated in a mice TSA tumor model using multimodal (PET/MRI/optical) imaging.

Published
2019

43. Treatment of multiple brain metastases using gadolinium nanoparticles and radiotherapy: NANO-RAD, a phase I study protocol

Author

Sandrine Dufort, Olivier Tillement, Jean-Louis Quesada, Josiane Arnaud, Sylvie Grand, Julie Villa, Jacques Balosso, Géraldine Le Duc, Christophe Mendoza, Lucie Sancey, François Lux, Camille Verry, Service de radiothérapie- CHU de Grenoble, CHU Grenoble, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), NH TherAguix SA [Meylan], Centre d'Investigation Clinique [Grenoble] (CIC Grenoble ), CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de neuroradiologie [Grenoble], Département de biologie intégrée, CHU Grenoble-Hôpital Michallon, Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de Biologie et Pathologie [CHU Grenoble] (IBP), CHU Grenoble-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Sancey, Lucie, and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Oncology, medicine.medical_specialty, Radiation-Sensitizing Agents, medicine.medical_treatment, [SDV]Life Sciences [q-bio], theranostic, Metal Nanoparticles, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gadolinium, Targeted therapy, Neoplasms, Multiple Primary, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, [SDV.CAN] Life Sciences [q-bio]/Cancer, adult radiotherapy, Internal medicine, brain metastases, medicine, Protocol, Distribution (pharmacology), 030212 general & internal medicine, Protocol (science), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Clinical Trials, Phase I as Topic, Radiotherapy, business.industry, Brain Neoplasms, Cancer, General Medicine, medicine.disease, Combined Modality Therapy, Magnetic Resonance Imaging, 3. Good health, Radiation therapy, [SDV] Life Sciences [q-bio], Treatment Outcome, Tolerability, Toxicity, gadolinium nanoparticle, Dose Fractionation, Radiation, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

IntroductionOccurrence of multiple brain metastases is a critical evolution of many cancers with significant neurological and overall survival consequences, despite new targeted therapy and standard whole brain radiotherapy (WBRT). A gadolinium-based nanoparticle, AGuIX, has recently demonstrated its effectiveness as theranostic and radiosensitiser agent in preclinical studies. The favourable toxicity profile in animals and its administration as a simple intravenous injection has motivated its use in patients with this first in human study.Methods and analysisThe NANO-RAD study is a phase I, first in human injection, monocentric, open-label, dose-escalation study to investigate the safety, the tolerability and the spectrum of side effects of AGuIX in combination with WBRT (30 Gy, 10 fractions of 3 Gy) for patients with multiple brain metastases. Five dose escalation cohorts are planned: 15, 30, 50, 75 and 100 mg/kg. A total of 15–18 patients will be recruited into this trial. The primary objective is to determine the maximum-tolerated dose of AGuIX nanoparticles combined with WBRT for the treatment of multiple brain metastases. Toxicity will be assessed using the National Cancer Institute Common Toxicity Criteria V.4.03. Secondary objectives are pharmacokinetic profile, distribution of AGuIX in metastases and surrounding healthy tissue visualised by MRI, intracranial progression-free survival and overall survival. Intracranial response will be determined according to Response Evaluation Criteria in Solid Tumour Criteria V.1.1 comparing MRI performed prior to treatment and at each follow-up visits.Ethics and disseminationApproval was obtained from the ethics committee Sud Est V, France (Reference number 15-CHUG-48). The study was approved by the French National Agency for the Safety of Medicines and Health Products (ANSM) (Reference number 151519A-12). The results will be published in peer-reviewed journals or disseminated through national and international conferences.Trial registration numberNCT02820454; Pre-results.

Published
2019

44. La médecine de précision en oncologie : challenges, enjeux et nouveaux paradigmes

Author

Patrice Denèfle, Stéphanie Cox, Marina Rousseau-Tsangaris, Arnaud Cutivet, Olivier Tredan, Hai-Ha Le, Robert Gardette, Stéphane Dalle, Nancy Abou-Zeid, Larisa Lerner, Brenda Bogaert, Shady Kotb, Yusuf Baran, Pierre Leurent, Jean-Yves Blay, Jean-Marc Holder, Alberto Cambrosio, Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Voluntis, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de recherches philosophiques de Lyon (IRPhiL), Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), SeqOne [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Biologie Computationnelle (IBC), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Department of Social Studies of Medicine (SSOM), McGill University = Université McGill [Montréal, Canada], and Centre de Psychiatrie et Neurosciences (U894)

Subjects
Cancer Research, Oncology, Radiology, Nuclear Medicine and imaging, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, General Medicine
Abstract

International audience; L’oncologie médicale a pris, depuis quelques années, un tournant substantiel en intégrant la dimension génomique dans la prise de décision thérapeutique. En raison de l’accès aux technologies de séquençage (exome complet, séquençage ciblé du génome, séquençage de l’ARN, ADN circulant…) facilité par la mise en place de plateformes de biologie moléculaire et la diminution des coûts par échantillon, la caractérisation moléculaire est devenue un outil supplémentaire à la disposition du clinicien, s’ajoutant au diagnostic histologique et immunohistochimique et aux données d’imagerie radiologique. Cette approche moléculaire a permis d’identifier de nouvelles formes nosologiques et permet, au-delà de l’aspect cognitif, de renseigner sur les altérations qui sont à prendre en compte dans les décisions thérapeutiques (biomarqueurs prédictifs, activation de voies spécifiques, mutations de résistance). C’est dans ce contexte de profond et rapide changement de pratique médicale et scientifique qu’il a été proposé de réfléchir collectivement aux nouveaux enjeux sous la forme d’un workshop à l’occasion de Biovision qui s’est tenu à Lyon, du 4 au 6 avril 2017. Biovision est un forum international dédié à la Santé et aux Sciences de la vie, qui réunit sur quelques jours des communautés scientifiques, académiques et industrielles dans le but d’accélérer l’innovation. Lors de la 12e édition en avril 2017, le CLARA, l’Institut Roche ainsi que le SIRIC de Lyon ont donc organisé un workshop autour de la médecine de précision (« Precision medicine in oncology: challenges, stakes and new paradigms »). Des experts ainsi que des participants de différents horizons ont échangé sur le sujet afin de proposer des mesures clé.

Published
2019

45. Selective Priming of Tumor Blood Vessels by Radiation Therapy Enhances Nanodrug Delivery

Author

Kunjachan, Sijumon, Kotb, Shady, Pola, Robert, Pechar, Michal, Kumar, Rajiv, Singh, Bijay, Gremse, Felix, Taleeli, Reza, Trichard, Florian, Motto-Ros, Vincent, Sancey, Lucie, Detappe, Alexandre, Yasmin-Karim, Sayeda, Protti, Andrea, Shanmugam, Ilanchezhian, Ireland, Thomas, Etrych, Tomas, Sridhar, Srinivas, Tillement, Olivier, Makrigiorgos, Mike, Berbeco, Ross, Department of Radiation Oncology, Department of RBrigham and Women’s Hospital, Dana-Farber Cancer Institute, and Harvard Medical School, Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institute of Macromolecular Chemistry [Prague] (IMC), Czech Academy of Sciences [Prague] (ASCR), Nanomedicine Science and Technology Center and Department of Physics, Northeastern University [Boston], Experimental Molecular Imaging, University Hospital and Helmholtz Institute for Biomedical Engineering, Division of Medical Physics & Engineering, University of Texas Southwestern Medical Center, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Lurie Family Imaging Center, Dana-Farber Cancer Institute and Harvard Medical School, A-ICP-MS, Department of Earth and Environmental Sciences, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institute of Macromolecular Chemistry of the Czech Academy of Sciences (IMC / CAS), Czech Academy of Sciences [Prague] (CAS), Spectrométrie des biomolécules et agrégats (SPECTROBIO), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), LA-ICP-MS Department, Department of Earth and Environment [Boston], Boston University [Boston] (BU)-Boston University [Boston] (BU), Rayet, Béatrice, and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Nanoscale materials, Neovascularization, Pathologic, Radiotherapy, Optical Imaging, lcsh:R, Metal Nanoparticles, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neoplasms, Experimental, Article, Mice, Drug Delivery Systems, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Drug delivery, Human Umbilical Vein Endothelial Cells, Animals, Humans, lcsh:Q, Gold, lcsh:Science, ddc:600, Magnetic Resonance Angiography
Abstract

International audience; Effective drug delivery is restricted by pathophysiological barriers in solid tumors. In human pancreatic adenocarcinoma, poorly-permeable blood vessels limit the intratumoral permeation and penetration of chemo or nanotherapeutic drugs. New and clinically viable strategies are urgently sought to breach the neoplastic barriers that prevent effective drug delivery. Here, we present an original idea to boost drug delivery by selectively knocking down the tumor vascular barrier in a human pancreatic cancer model. Clinical radiation activates the tumor endothelial-targeted gold nanoparticles to induce a physical vascular damage due to the high photoelectric interactions. Active modulation of these tumor neovessels lead to distinct changes in tumor vascular permeability. Noninvasive MRI and fluorescence studies, using a short-circulating nanocarrier with MR-sensitive gadolinium and a long-circulating nanocarrier with fluorescence-sensitive nearinfrared dye, demonstrate more than two-fold increase in nanodrug delivery, post tumor vascular modulation. Functional changes in altered tumor blood vessels and its downstream parameters, particularly, changes in Ktrans (permeability), Kep (flux rate), and Ve (extracellular interstitial volume), reflect changes that relate to augmented drug delivery. The proposed dual-targeted therapy effectively invades the tumor vascular barrier and improve nanodrug delivery in a human pancreatic tumor model and it may also be applied to other nonresectable, intransigent tumors that barely respond to standard drug therapies.

Published
2019

46. Self-crosslinked fibrous collagen/chitosan blends: Processing, properties evaluation and monitoring of degradation by bi-fluorescence imaging

Author

Martine Renard, Helene Gehan, E. Chereul, Guillaume Sudre, Lionel Marcon, N. Boucard, François Lux, M. Meulle, M. Durand, Laurent David, M. Vandesteene, Quentin Denost, P.N. Oliveira, L. Bordenave, Samantha Roques, Pierre Alcouffe, Alexandra Montembault, M. Vandamme, K. Albespy, V. Centis, D. Campos, CCSD, Accord Elsevier, Ingénierie des Matériaux Polymères (IMP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Biom'up, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), VOXCAN, MDB Texinov (MDB Texinov), MDB Texinov, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
Fluorescence-lifetime imaging microscopy, [CHIM.POLY] Chemical Sciences/Polymers, Collagen:chitosan scaffolds, Chemical Phenomena, Cell Survival, Biocompatible Materials, 02 engineering and technology, Biochemistry, Chitosan, Mice, 03 medical and health sciences, chemistry.chemical_compound, Tissue engineering, Structural Biology, Materials Testing, Spectroscopy, Fourier Transform Infrared, [CHIM] Chemical Sciences, Animals, [CHIM]Chemical Sciences, Sample preparation, Fourier transform infrared spectroscopy, Molecular Biology, Mechanical Phenomena, 030304 developmental biology, 0303 health sciences, Tissue Scaffolds, Chemistry, Optical Imaging, technology, industry, and agriculture, Bi-fluorescence imaging, General Medicine, Dehydrothermal treatment, 021001 nanoscience & nanotechnology, Fluorescence, Thermogravimetry, [CHIM.POLY]Chemical Sciences/Polymers, Chemical engineering, Covalent bond, Collagen, 0210 nano-technology
Abstract

International audience; Porous collagen/chitosan scaffolds with different Collagen:Chitosan (Coll:Ch) ratios were prepared by freeze-drying followed by self-crosslinking via dehydrothermal treatment (DHT) and characterized as biomaterials for tissue engineering. Cy7 and Cy5.5 fluorochromes were covalently grafted to collagen and chitosan, respectively. Thus, it was possible, using optical fluorescence imaging of the two fluorochromes, to simultaneously track their in vivo biodegradation, in a blend scaffold form. The fluorescence signal evolution, due to the bioresorption, corroborated with histological analysis. In vitro cytocompatibility of Coll:Ch blend scaffolds were evaluated with standardized tests. In addition, the scaffolds showed a highly interconnected porous structure. Extent of crosslinking was analyzed by convergent analysis using thermogravimetry, Fourier Transform Infrared Spectroscopy and PBS uptake. The variations observed with these techniques indicate strong interactions between collagen and chitosan (covalent and hydrogen bonds) promoted by the DHT. The mechanical properties were characterized to elucidate the impact of the different processing steps in the sample preparation (DHT, neutralization and sterilization by β-irradiation) and showed a robust processing scheme with low impact of Coll:Ch composition ratio.

Published
2019

47. AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine

Author

Camille Verry, Awatef Allouch, Carolyn J. Anderson, Olivier Tillement, Cyrus Chargari, Nathalie Mignet, Benoit Larrat, Marc Janier, Jacqueline Sidi-Boumedine, Kevin M. Prise, Peter Fries, Bich-Thuy Doan, Erika Porcel, Fabien Rossetti, Jacques Balosso, Marie-Caline Abadjian, Dominique Ardail, Frédéric Boschetti, Yannick Crémillieux, Alexandre Detappe, Claire Rodriguez-Lafrasse, Ross Berbeco, Marie-Thérèse Aloy, Sébastien Mériaux, Vu Long Tran, Emmanuel L. Barbier, Sandrine Lacombe, Sandrine Dufort, Matteo Martini, Andreas Müller, Eric Deutsch, Karl T. Butterworth, Emmanuelle Canet-Soulas, Géraldine Le Duc, Franck Denat, Goran Angelovski, Guillaume Bort, Céline Frochot, Jean-Luc Perfettini, Eloise Thomas, Stéphane Roux, Tristan Doussineau, Muriel Barberi-Heyob, Michael J. Evans, François Lux, Charles Truillet, Stephen J. McMahon, Penelope Bouziotis, Thomas, Noémie, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), NH TherAguix SA [Meylan], Nano-H SAS, Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CheMatech - Macrocycle Design Technologies, Max Planck Institute for Biological Cybernetics, Max-Planck-Gesellschaft, Dana-Farber Cancer Institute [Boston], Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Université Paris sciences et lettres (PSL), Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Clinic for Diagnostic and Interventional Radiology, Saarland University Medical Center, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Center for Scientific Research 'Demokritos' (NCSR), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Réactions et Génie des Procédés (LRGP), Rayonnement synchrotron et Recherche Médicale, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), University of California [San Francisco] (UC San Francisco), University of California (UC), Université de Lyon, Centre for Cancer Research and Cell Biology, Queen's University [Belfast] (QUB), PRISME (PRISME), Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire de Lyon (IPNL), Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Radiothérapie moléculaire (UMR 1030), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Curiethérapie, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR), Institut de Recherche Biomédicale des Armées (IRBA), French Military Health Service Academy, École du Val de Grâce (EVDG), Service de Santé des Armées-Service de Santé des Armées, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), University of California [San Francisco] (UCSF), University of California, Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), NH Theraguix, Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Service Hospitalier Frédéric Joliot (SHFJ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Résonance magnétique des systèmes biologiques (RMSB), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Paris Sciences et Lettres (PSL), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Equipe 6 : Rayonnement synchrotron et Recherche Médicale, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-[GIN] Grenoble Institut des Neurosciences, Université Paris-Sud 11 - Faculté de médecine (UP11 UFR Médecine), Ecole du Val-de-Grâce, UM Biochimie des Cancers et Biothérapies, CHU Grenoble-Institut de Biologie et Pathologie, Institut Européen des membranes (IEM), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS), Institut Galien Paris-Sud (IGPS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie et de Spectroscopie (LRMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de Mécanique et Technologie (LMT), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Institute of Computer Science VI, Université Henri Poincaré - Nancy 1 (UHP)-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS), Rhône-Alpes Research Program on Hadrontherapy, National French Hadrontherapy Centre - Etoile, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurorestoration Group, King‘s College London-Wolfson Centre for Age-related Diseases, Ciblage thérapeutique en Oncologie (EA3738), Unité Médicale d'Oncologie Moléculaire et Transfert (UMOMT), Hospices Civils de Lyon (HCL), Laboratoire des collisions atomiques et moléculaires (LCAM), Service d'oncologie-radiothérapie, Hôpital d'Instruction des Armées du Val de Grâce, Service de Santé des Armées, and European Synchrotron Radiation Facility (ESRF)

Subjects
Radiation-Sensitizing Agents, Gadolinium, medicine.medical_treatment, 02 engineering and technology, Review Article, Pharmacology, Theranostic Nanomedicine, Mice, 0302 clinical medicine, Melanoma, Brain Neoplasms, General Medicine, [CHIM.MATE]Chemical Sciences/Material chemistry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 021001 nanoscience & nanotechnology, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Nuclear Medicine & Medical Imaging, Radiology Nuclear Medicine and imaging, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Toxicity, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, Clinical Sciences, chemistry.chemical_element, [SDV.CAN]Life Sciences [q-bio]/Cancer, Enhanced permeability and retention effect, 03 medical and health sciences, SDG 3 - Good Health and Well-being, [SDV.CAN] Life Sciences [q-bio]/Cancer, In vivo, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, medicine, Animals, Humans, Radiology, Nuclear Medicine and imaging, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, Cancer, medicine.disease, Radiation therapy, Clinical trial, chemistry, Nanoparticles, business, Forecasting
Abstract

International audience; AGuIX® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates. This nanoparticle has been recently accepted in clinical trials in association with radiotherapy. This review will summarize the principal preclinical results that have led to first in man administration. No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys). Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration. High radiosensitizing effect has been observed with different types of irradiations in vitro and in vivo on a large number of cancer types (brain, lung, melanoma, head and neck…). The review concludes with the second generation of AGuIX nanoparticles and the first preliminary results on human.

Published
2019

48. Are Fluorescent Silicon Nanoparticles Formed in a One-Pot Aqueous Synthesis?

Author

Sergei Alekseev, Dmytro Korytko, Vladimir Lysenko, Bohdan V. Oliinyk, Taras Shevchenko National University of Kyiv, Surfaces, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), INL - Spectroscopies et Nanomatériaux (INL - S&N), Institut des Nanotechnologies de Lyon (INL), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-École Centrale de Lyon (ECL), Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
Materials science, Aqueous solution, Silicon, General Chemical Engineering, Nanoparticle, chemistry.chemical_element, [CHIM.MATE]Chemical Sciences/Material chemistry, 02 engineering and technology, General Chemistry, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, Fluorescence, 0104 chemical sciences, chemistry, TRISODIUM CITRATE DIHYDRATE, Microwave heating, Materials Chemistry, 0210 nano-technology, Nuclear chemistry
Abstract

International audience; Critical analysis of the data reported by Zhong et al. (J. Am. Chem. Soc.2013, 135 (22), 8350–8356) is carried out. In particular, one of the main results of Zhong et al. concerning the formation of photoluminescent silicon nanoparticles (Si NPs) in an aqueous solution of (3-aminopropyl)trimethoxysilane (APTMS) and trisodium citrate dihydrate (Na3Cit) under microwave heating is impugned. These results are reconsidered here because of what appear to be significant inaccuracies and misinterpretations that have been spread through a wide number of other subsequent publications.

Published
2019
Full Text
View/download PDF

49. Kinetics of Hydrogen Generation from Oxidation of Hydrogenated Silicon Nanocrystals in Aqueous Solutions

Author

Sergii Tutashkonko, Tetyana Nychyporuk, A.I. Manilov, Valeriy A. Skryshevsky, Vladimir Lysenko, Gulshat Amirkhanova, G.K. Mussabek, Sergei V Litvinenko, Yerkin Shabdan, Sergei Alekseev, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Al-Farabi Kazakh National University [Almaty] (KazNU), Institute of Information and Computational Technologies (IICT), Taras Shevchenko National University of Kyiv, Institute of High Technologies [Kyiv], Institut des Nanotechnologies de Lyon (INL), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-École Centrale de Lyon (ECL), Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE), INL - Photovoltaïque (INL - PV), and Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon)

Subjects
Materials science, Silicon, Hydrogen, 020209 energy, General Chemical Engineering, chemistry.chemical_element, 02 engineering and technology, Porous silicon, 7. Clean energy, Redox, Article, [SPI.MAT]Engineering Sciences [physics]/Materials, lcsh:Chemistry, [SPI]Engineering Sciences [physics], nanosilicon oxidation, engineering of silicon nanoparticles, Oxidizing agent, 0202 electrical engineering, electronic engineering, information engineering, Molecule, hydrogen generation rate, General Materials Science, Physics::Atomic Physics, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, Hydrogen production, 021001 nanoscience & nanotechnology, porous silicon nanopowder, lcsh:QD1-999, chemistry, Chemical engineering, Hydrogen fuel, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], 0210 nano-technology
Abstract

Hydrogen generation rate is one of the most important parameters which must be considered for the development of engineering solutions in the field of hydrogen energy applications. In this paper, the kinetics of hydrogen generation from oxidation of hydrogenated porous silicon nanopowders in water are analyzed in detail. The splitting of the Si-H bonds of the nanopowders and water molecules during the oxidation reaction results in powerful hydrogen generation. The described technology is shown to be perfectly tunable and allows us to manage the kinetics by: (i) varying size distribution and porosity of silicon nanoparticles, (ii) chemical composition of oxidizing solutions, (iii) ambient temperature. In particular, hydrogen release below 0 &deg, C is one of the significant advantages of such a technological way of performing hydrogen generation.

Published
2020

50. Human Serum Albumin in the Presence of AGuIX Nanoagents: Structure Stabilisation without Direct Interaction

Author

Jean Philippe Renault, Olivier Tillement, Sandrine Lacombe, Frank Wien, Daniela Salado-Leza, François Lux, Serge Pin, Erika Porcel, Xiaomin Yang, Laurent Marichal, Marta Bolsa-Ferruz, Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interdisciplinaire sur l'Organisation Nanométrique et Supramoléculaire (LIONS), Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M) (NIMBE UMR 3685), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Cátedras CONACYT, Consejo Nacional de Ciencia y Tecnología [Mexico] (CONACYT), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Synchrotron SOLEIL, the China Scholarship Council (CSC, N 201607040068), Université Paris Saclay via the 'Inititative de Recherche Stratégique' program, grant IRS NanoTheRad project, ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), European Project: 608163,EC:FP7:PEOPLE,FP7-PEOPLE-2013-ITN,ARGENT(2014), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
Circular dichroism, Radiosensitizer, Gadolinium, Contrast Media, chemistry.chemical_element, 02 engineering and technology, Calorimetry, 010402 general chemistry, 01 natural sciences, Article, Catalysis, lcsh:Chemistry, Inorganic Chemistry, Toxicity Tests, medicine, Humans, structure, Physical and Theoretical Chemistry, lcsh:QH301-705.5, Molecular Biology, Serum Albumin, Spectroscopy, nanoparticle, Organic Chemistry, Albumin, [CHIM.MATE]Chemical Sciences/Material chemistry, General Medicine, stability, 021001 nanoscience & nanotechnology, Human serum albumin, Blood proteins, Fluorescence, circular dichroism, 0104 chemical sciences, 3. Good health, Computer Science Applications, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Spectrometry, Fluorescence, lcsh:Biology (General), lcsh:QD1-999, chemistry, Biophysics, Nanoparticles, gadolinium, High ratio, protein, 0210 nano-technology, medicine.drug
Abstract

The gadolinium-based nanoagent named AGuIX&reg, is a unique radiosensitizer and contrast agent which improves the performance of radiotherapy and medical imaging. Currently tested in clinical trials, AGuIX&reg, is administrated to patients via intravenous injection. The presence of nanoparticles in the blood stream may induce harmful effects due to undesired interactions with blood components. Thus, there is an emerging need to understand the impact of these nanoagents when meeting blood proteins. In this work, the influence of nanoagents on the structure and stability of the most abundant blood protein, human serum albumin, is presented. Synchrotron radiation circular dichroism showed that AGuIX&reg, does not bind to the protein, even at the high ratio of 45 nanoparticles per protein at 3 mg/L. However, it increases the stability of the albumin. Isothermal thermodynamic calorimetry and fluorescence emission spectroscopy demonstrated that the effect is due to preferential hydration processes. Thus, this study confirms that intravenous injection of AGuIX&reg, presents limited risks of perturbing the blood stream. In a wider view, the methodology developed in this work may be applied to rapidly evaluate the impact and risk of other nano-products that could come into contact with the bloodstream.

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results