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Iron oxide nanoparticles (IONPs) are suitable materials for contrast enhancement in magnetic resonance imaging (MRI). Their potential clinical applications range from diagnosis to therapy and follow‐up treatments. However, a deeper understanding of the interaction between IONPs, culture media and cells is necessary for expanding the application of this technology to different types of cancer therapies. To achieve new insights of these interactions, a set of IONPs were prepared with the same inorganic core and five distinct coatings, to study their aggregation and interactions in different physiological media, as well as their cell labelling efficiency. Then, a second set of IONPs, with six different core sizes and the same coating, were used to study how the core size affects cell labelling and MRI in vitro. Here, IONPs suspended in biological media experience a partial removal of the coating and adhesion of molecules. The FBS concentration alters the labelling of all types of IONPs and hydrodynamic sizes ≥ 300 nm provide the greatest labelling using the centrifugation‐mediated internalization (CMI). The best contrast for MRI results requires a core size range between 12–14 nm coated with dimercaptosuccinic acid (DMSA) producing R2* values of 393.7 s−1 and 428.3 s−1, respectively. These findings will help to bring IONPs as negative contrast agents into clinical settings. post-print 2.788 KB

In recent years, magnetic nanoparticles have been widely investigated due to their potential in biomedical applications. For successful in vivo applications, magnetic nanoparticles must satisfy several requirements such as biocompatibility, invisibility to the immune system, high colloidal stability in biological fluids, and long blood circulation times. In this study, we have developed a formulation in which the magnetic nanoparticles are coated with bovine serum albumin to provide enhanced colloidal stability in biological fluids preserving their magnetic properties. In addition, the nanoparticles carry a chemotherapeutic drug, showing their potential as drug delivery systems. Our results reveal the influence of protein adsorption on the colloidal stability and the dynamical magnetic response of functionalized magnetic nanoparticles. Moreover, cellular internalization and in vitro cytotoxic activity in Panc-1 pancreatic cancer cells reveal enhanced cellular internalization, successful intracellular drug delivery, and efficient anticancer activity.

[EN] Optical trapping of individual particles is believed to be only effective under highly focused beams because these conditions strengthen the gradient forces. This is especially critical in the beam propagating direction, where the scattering and absorption forces must be counterbalanced. Here, we demonstrate that optical trapping of nanostructures is also possible in a weakly focused beam. We study the theoretical conditions for effective three-dimensional optical confinement and verify them experimentally on iron-oxide-based nanoparticles with and without a silica coating, for which scattering, absorption, and gradient forces exist. This chemical approach to their all-optical control is, in turn, convenient for making magnetic nanostructures biocompatible. Weakly focused beams reduce the irradiance in the focal region and therefore the photon damage to the samples, which is further important to delay quantum dot quenching in the trap or to prevent artifacts in the study of biomolecular motor dynamics., We are grateful to Dr. Maria Acebron and Dr. Beatriz H. Juarez for their support in the silica encapsulation of the nano particles. This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO, Grant MAT2015-71806-R). IMDEA Nanociencia acknowledges support from the "Severo Ochoa" Programme for Centers of Excellence in R&D (MINECO, Grant SEV-2016-0686). H.R.-R. is supported by an FPI-UAM fellowship.

Magnetic nanoparticles (MNPs), and in particular iron oxide nanoparticles (mainly magnetite and maghemite), are being widely used in the form of aqueous colloids for biomedical applications. In such colloids, nanoparticles tend to form assemblies, either aggregates, if the union is permanent, or agglomerates, if it is reversible. These clustering processes have a strong impact on the MNPs' properties that are often not well understood. In this review, the causes and consequences of MNPs aggregation/agglomeration are reviewed and discussed. Special attention has been paid to the impact of the MNPs aggregation/agglomeration on their magnetic properties and heating properties, when exposed to an alternating magnetic field in the frame of magnetic hyperthermia. In addition, a model system with MNPs of two different sizes coated with three different molecules oleic acid, meso-2, 3-dimercaptosuccinic acid and poly(maleic anhydride-alt-1-octadecene) has been characterized and the results used to support the ideas reviewed., This work was supported by Fondo Social de la DGA (grupos DGA, BIONANOSURF), Ministerio de la Economía y Competitividad del Gobierno de España for the public funding of Proyectos I+D+I—Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad (projects MAT2017-88148-R, MAT2015-71806-R and SAF2014-54763-C2-2-R), Comunidad de Madrid (Project NANOFRONTMAG-CM, S2013/MIT-2850), and ERCStarting Grant 239931-NANOPUZZLE. IMDEA Nanociencia acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686). LG acknowledges financial support from the Ramón y Cajal subprogram (RYC-2014-15512).

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid. Fecha de lectura: 10-2-2017.

Pyramidal CdSe NCs self-assembled on highly oriented pyrolytic graphite (HOPG) substrates were characterized, both by STM and synchrotron XPS measurements, upon annealing treatments at different temperatures. By STM, shape modifications at different temperatures was observed. In particular the NCs experience a shape relaxation via an intra-particle ripening or physical coagulation after exposing the sample at 200°C, while a mass transfer via inter-particle ripening (Ostwald ripening) is activated at 400°C. Synchrotron XPS data allow establishing a clear differentiation between the desorption behavior of long octadecylphosphonic acid-related ligands and short chloride ionic ligands., B.H.J. thanks for funding under the frame of the following projects: S2013/MIT‐2740 from Comunidad de Madrid, FIS2012‐33011, FIS2015‐67367‐C2‐1‐P, and MAT2013‐47395‐C4‐3‐R, from the Spanish Ministry of Economy and Competitiveness. R.O. thanks for FIS2012‐33011 and FIS2015‐67367‐C2‐1‐P.

Nanotechnology plays an increasingly important role in the biomedical arena. Iron oxide nanoparticles (IONPs)-labelled cells is one of the most promising approaches for a fast and reliable evaluation of grafted cells in both preclinical studies and clinical trials. Current procedures to label living cells with IONPs are based on direct incubation or physical approaches based on magnetic or electrical fields, which always display very low cellular uptake efficiencies. Here we show that centrifugation-mediated internalization (CMI) promotes a high uptake of IONPs in glioblastoma tumour cells, just in a few minutes, and via clathrin-independent endocytosis pathway. CMI results in controllable cellular uptake efficiencies at least three orders of magnitude larger than current procedures. Similar trends are found in human mesenchymal stem cells, thereby demonstrating the general feasibility of the methodology, which is easily transferable to any laboratory with great potential for the development of improved biomedical applications.

The most prevalent image of the morphology of Au-CdSe hybrid nanoparticles (HNPs) is that of dumbbells or matchsticks with CdSe nanoparticles (NPs) acting as seed material onto which spherical Au dots are deposited. On the basis of a system with only three reaction components, CdSe seeds, n-dodecyltrimethylammonium bromide-complexed AuCl, and dodecanethiol, we demonstrate how the morphology of the Au deposits on the semiconductor NPs, either in the form of dots on the vertices or in the form of a shell around the NP surface, can be determined by controlling the oxidation state of the metal precursor. Furthermore, we apply X-ray photoelectron spectroscopy to show that the resultant deposits are composed of partially oxidized Au, corresponding to a Au-Se compound regardless the deposit morphology. To obtain a detailed characterization of the HNPs with different morphologies and to gain mechanistic insights into the deposition process, (cryogenic) high-resolution transmission electron microscopy, mass spectrometry, cyclic voltammetry, and computational simulations have been performed. Our results emphasize that the knowledge of the surface chemistry of the seed particles as well as a defined picture of the metal precursors is necessary to understand heterodeposition processes., C.K. and M.M. acknowledge the European Union for the ERC Starting Grant 2D-SYNETRA (304980, Seventh Framework Program FP7) and the Deutsche Forschungsgemeinschaft for granting the project KL 1453/9-1. B.H.J. is thankful for funding in the frame of the following projects: S2013/MIT2740 from Comunidad de Madrid and FIS2012-33011 and MAT2013-47395-C4-3-R and FIS2015-67367-C2-1-P from the Spanish Ministry of Economy and Competitiveness. R.O. is thankful for FIS2012-33011. Furthermore, the authors thank the Helmholtz Zentrum Berlin to have benn granted access to the BESSY-II facility, in particular the SurICat UHV XPS station. N.G.B. acknowledges financial support by MINECO through the Ramon y Cajal program (RYC-2012- 10991) and by the European Commission Seventh Framework Programme (FP7) through the Marie Curie Career Integration Grant (322153-MINE).

Breakthroughs in nanotechnology have made it possible to integrate different nanoparticles in one single hybrid nanostructure (HNS), constituting multifunctional nanosized sensors, carriers, and probes with great potential in the life sciences. In addition, such nanostructures could also offer therapeutic capabilities to achieve a wider variety of multifunctionalities. In this work, the encapsulation of both magnetic and infrared emitting nanoparticles into a polymeric matrix leads to a magnetic-fluorescent HNS with multimodal magnetic-fluorescent imaging abilities. The magnetic-fluorescent HNS are capable of simultaneous magnetic resonance imaging and deep tissue infrared fluorescence imaging, overcoming the tissue penetration limits of classical visible-light based optical imaging as reported here in living mice. Additionally, their applicability for magnetic heating in potential hyperthermia treatments is assessed.

Nanotechnology plays an increasingly important role in the biomedical arena. Iron oxide nanoparticles (IONPs)-labelled cells is one of the most promising approaches for a fast and reliable evaluation of grafted cells in both preclinical studies and clinical trials. Current procedures to label living cells with IONPs are based on direct incubation or physical approaches based on magnetic or electrical fields, which always display very low cellular uptake efficiencies. Here we show that centrifugation-mediated internalization (CMI) promotes a high uptake of IONPs in glioblastoma tumour cells, just in a few minutes and via clathrin-independent endocytosis pathway. CMI results in controllable cellular uptake efficiencies at least three orders of magnitude larger than current procedures. Similar trends are found in human mesenchymal stem cells, thereby demonstrating the general feasibility of the methodology, which is easily transferable to any laboratory with great potential for the development of improved biomedical applications.

Rod-like octadecylphosphonic acid (ODPA) capped CdSe nanocrystals (NCs) produced by hot injection in the presence of chlorinated cosolvents modify their shape and surface properties by incorporation of chloride in the capping ligand shell. Correlated cyclic voltammetry (CV) and X-ray photoelectron spectroscopy (XPS) studies have been performed to address the effect of this incorporation on the NCs surface. In contrast to ODPA capped rod-like NCs, the XPS studies confirm that, during the oxidation of NCs containing chloride, not only the oxidation of Se surface atoms but also of Cd atoms takes place. Furthermore, XPS studies also confirm the partial reversibility of the Se oxidation in the presence of chloride. Both CV and subsequent XPS measurements allows identifying chemical environments and surface site modifications, essential to understand the stability and performance of NCs acting as active layers in optoelectronic devices. © 2014 American Chemical Society., Financial support from the Ministerio de Ciencia e Innovación (FIS2012-33011 is gratefully acknowledged). L.d.l.C. acknowledges Research Grants and contracts at IMDEA Nanoscience.

The performance of devices based on semiconductor nanocrystals (NCs) improves both with stronger interface interactions among NCs and between NCs and solid electrode surfaces. The combination of X-ray photoelectron spectroscopy (XPS) and solid 31P CP/MAS NMR (cross-polarization/magic angle spinning nuclear magnetic resonance) shows that the selective substitution of long organic chains by chlorine atomic ligands during the colloidal synthesis by the hot injection method promotes the adsorption of CdSe NCs to carbon sp 2 surfaces, leading to the formation of well-ordered NC monolayers on graphitic materials. © 2013 American Chemical Society., B.H.J. thanks the European Commission for FP7-PEOPLE-ERG-2008 (239256), the former Spanish Ministry of Science and Innovation for RYC-2007-01709 and MAT-2009-13488. C.K. and M.M. acknowledge the Deutsche Forschungsgemeinschaft (DFG) for financial support. Financial support from the Ministerio de Ciencia e Innovación (FIS2010-18847, FIS2012-33011 and Consolider-Ingenio en Nanociencia Molecular, ref CSD200700010), Comunidad de Madrid (Grant S2009/MAT-1726) and EU (SMALL, PITN-GA-2009-23884) is gratefully acknowledged.

This is the peer reviewed version of the following article: Ortgies, Dirk H., Teran, Francisco J. Rocha, Uéslen, Cueva, Leonar de la, Salas, Gorka, cabrera, David, Vanetsev, Alexander S., Rähn, Mikhel, Väino,Sammelselg, Orlosvkii, Yurii V. and Jaque, Daneil "Optomagnetic nanoplatforms for in situ controlled hyperthermia" Advances Funtcional Materials 28.11 (2018) which has been published in final form at http://doi.org/10.1002/adfm.201704434. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.", Magnetic nanoparticles (M:NPs) are unique agents for in vivo thermal therapies due to their multimodal capacity for efficient heat generation under optical and/or magnetic excitation. Nevertheless, their transfer from laboratory to the clinic is hampered by the absence of thermal feedback and by the influence that external conditions (e.g., agglomeration and biological matrix interactions) have on their heating efficiency. Overcoming these limitations requires, first, the implementation of strategies providing thermal sensing to M:NPs in order to obtain in situ thermal feedback during thermal therapies. At the same time, M:NPs should be modified so that their heating efficiency will be maintained independently of the environment and the added capability for thermometry. In this work, optomagnetic hybrid nanostructures (OMHSs) that simultaneously satisfy these two conditions are presented. Polymeric encapsulation of M:NPs with neodymium-doped nanoparticles results in a hybrid structure capable of subtissue thermal feedback while making the heating efficiency of M:NPs independent of the medium. The potential application of the OMHSs herein developed for fully controlled thermal therapies is demonstrated by an ex vivo endoscope-assisted controlled intracoronary heating experiment, This work was supported by the Spanish Ministry of Economy and Competitiveness under Projects # MAT2016-75362-C3-1-R, # MAT2015-71806-R and # MAT2013-47395-C4-3-R, the Comunidad de Madrid (NANOFRONTMAG-CM, S2013/MIT-2850), and through the Instituto de Salud Carlos III under Project # PI16/00812. This work has also received funding from European Union’s H2020 and FP7 programme (NOCANTHER, GA 685795). D.H.O. is grateful to the Spanish Ministry of Economy and Competitiveness for a Juan de la Cierva scholarship (FJCI-2014-21101) and F.J.T. for a Ramon y Cajal fellowship (RYC-2011-09617). COST Actions CM1403 and TD1402 (RADIOMAG) are also acknowledged. The synthesis and preliminary testing of the fluorescence properties of the LaF3:Nd(3%) NPs was supported by Project # 16-12-10077 of the Russian Science Foundation. Nonfluorescent characterization of the OMHSs was supported by projects IUT2-24 and IUT20-54 of the Estonian Ministry of Education and Research