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The use of radionuclides for targeted endoradiotherapy is a rapidly growing field in oncology. In particular, the focus on the biological effects of different radiation qualities is an important factor in understanding and implementing new therapies. Together with the combined approach of imaging and therapy, therapeutic nuclear medicine has made great progress recently. A par-ticular area of research is the use of alpha-emitting radionuclides, which have unique physical properties associated with outstanding advantages, e.g. for single tumor cell targeting. Here, recent results and open questions regarding the production of alpha-emitting isotopes, their chemical combination with carrier molecules and clinical experience from compassionate use reports and clinical trials are discussed.

Despite recent therapy advances and a better understanding of colon cancer biology, it remains one of the major causes of death. The cancer stem cells, associated with the progression, metastasis, and recurrence of colon cancer, play a major role in promoting the development of tumour and are found to be chemo resistant. The stroma of the tumour, which makes up the bulk of the tumour mass, is composed of the tumour microenvironment. With the advent of theranostic and the development of personalised medicine, miRNAs are becoming increasingly important in the context of colon malignancies. A holistic understanding of the regulatory roles of miRNAs in cancer cells and cancer stem cells will allow us to design effective strategies to regulate miRNAs, which could lead to improved clinical translation and creating a potent colon cancer treatment strategy. In this review paper, we briefly discuss the history of miRNA as well as the mechanisms of miRNA and cancer stem cells that contribute to the tumour growth, apoptosis, and advancement of colon cancer. The usefulness of miRNA in colorectal cancer theranostic is further concisely reviewed. We conclude by holding a stance in addressing the prospects and possibilities for miRNA by the disclosure of recent theranostic approaches aimed at eradicating cancer stem cells and enhancing overall cancer treatment outcomes., Funding agencies:DST Inspire research student grant 190963Chettinad academy of Research and Education 004/Regr/AR-Research/2022-05

In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were engineered with an organic coating composed of low molecular weight heparin (LMWH) and bovine serum albumin (BSA), providing heparin-based nanoparticle systems (LMWH@SPIONs). The purpose was to merge the properties of the heparin skeleton and an inorganic core to build up a targeted theranostic nanosystem, which was eventually enhanced by loading a chemotherapeutic agent. Iron oxide cores were prepared via the co-precipitation of iron salts in an alkaline environment and oleic acid (OA) capping. Dopamine (DA) was covalently linked to BSA and LMWH by amide linkages via carbodiimide coupling. The following ligand exchange reaction between the DA-BSA/DA-LMWH and OA was conducted in a biphasic system composed of water and hexane, affording LMWH@SPIONs stabilized in water by polystyrene sulfonate (PSS). Their size and morphology were investigated via dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The LMWH@SPIONs’ cytotoxicity was tested, showing marginal or no toxicity for samples prepared with PSS at concentrations of 50 µg/mL. Their inhibitory activity on the heparanase enzyme was measured, showing an effective inhibition at concentrations comparable to G4000 (N-desulfo-N-acetyl heparin, a non-anticoagulant and antiheparanase heparin derivative; Roneparstat). The LMWH@SPION encapsulation of paclitaxel (PTX) enhanced the antitumor effect of this chemotherapeutic on breast cancer cells, likely due to an improved internalization of the nanoformulated drug with respect to the free molecule. Lastly, time-domain NMR (TD-NMR) experiments were conducted on LMWH@SPIONs obtaining relaxivity values within the same order of magnitude as currently used commercial contrast agents.

Theranostic platform technologies for therapy and imaging

FAP-targeted radiopharmaceuticals represent a breakthrough in cancer imaging and a viable option for therapeutic applications. OncoFAP is an ultra-high-affinity ligand of FAP with a dissociation constant of 680 pM. OncoFAP has been recently discovered and clinically validated for PET imaging procedures in patients with solid malignancies. While more and more clinical validation is becoming available, the need for scalable and robust procedures for the preparation of this new class of radiopharmaceuticals continues to increase. In this article, we present the development of automated radiolabeling procedures for the preparation of OncoFAP-based radiopharmaceuticals for cancer imaging and therapy. A new series of [68Ga]Ga-OncoFAP, [177Lu]Lu-OncoFAP and [18F]AlF-OncoFAP was produced with high radiochemical yields. Chemical and biochemical characterization after radiolabeling confirmed its excellent stability, retention of high affinity for FAP and absence of radiolysis by-products. The in vivo biodistribution of [18F]AlF-NOTA-OncoFAP, a candidate for PET imaging procedures in patients, was assessed in mice bearing FAP-positive solid tumors. The product showed rapid accumulation in solid tumors, with an average of 6.6% ID/g one hour after systemic administration and excellent tumor-to-healthy organs ratio. We have developed simple, quick, safe and robust synthetic procedures for the preparation of theranostic OncoFAP-compounds based on Gallium-68, Lutetium-177 and Fluorine-18 using the commercially available FASTlab synthesis module.

Molecular targeting requires assessing several factors that come into play such as the location of the target, the choice of radionuclide, the inertness of the bifunctional chelate and stability of the covalently bound halogens, matching the residence time in the tumor with the physical half-life of the radionuclide, the scale and scope of the disease, and the absorbed dose sensitivity of the targeted tumor compared to normal tissue. The principles of molecular targeting are well established, but a paradigm shift from designing a medium-affinity radiotracer used to determine target density to designing a high-affinity, high-target density radioligand to maximize the target-to-nontarget ratio should increase the probability of detecting lesions smaller than the instrument resolution. Developing and validating a therapeutic radiopharmaceutical for a single target is necessary, but often not sufficient to produce a toxic event because of other mechanisms that are only partially understood. These include nontargeted effects due to radiation emitted from neighboring, targeted cells as well as bystander effects produced by the cellular processing of radiation not necessarily impinging on DNA. Both of these indirect consequences of cellular radiation could make a substantial contribution to the efficacy of targeted radionuclide therapy. These mechanisms should be exploited to optimize the efficacy of targeted radiotherapy and overcome the inefficiency of tumor control due to nonuniform distribution of radiation dose. The design approach to take advantage of the indirect consequences of cellular radiation depends heavily on further elucidation of the indirect effect. The successful combination of these two should lead to more effective nuclear radiotherapy.

Antimetastatic properties on both murine and human osteosarcoma cell lines (POS-1 and KHOS) have been evidenced using exopolysaccharide (EPS) derivatives, produced by Alteromonas infernus bacterium. These derivatives had no significant effect on the cell cycle neither a pro-apoptotic effect on osteosarcoma cells. Based on this observation, these EPSs could be employed as new drug delivery systems for therapeutic uses. A theranostic approach, i.e., combination of a predictive biomarker with a therapeutic agent, has been developed notably by combining with true pair of theranostic radionuclides, such as scandium 47Sc/44Sc. However, it is crucial to ensure that, once complexation is done, the biological properties of the vector remain intact, allowing the molecular tropism of the ligand to recognize its molecular target. It is important to assess if the biological properties of EPS evidenced on osteosarcoma cell lines remain when scandium is complexed to the polymers and can be extended to other cancer cell types. Scandium-EPS complexes were thus tested in vitro on human cell lines: MNNG/HOS osteosarcoma, A375 melanoma, A549 lung adenocarcinoma, U251 glioma, MDA231 breast cancer, and Caco2 colon cancer cells. An xCELLigence Real Cell Time Analysis (RTCA) technology assay was used to monitor for 160 h, the proliferation kinetics of the different cell lines. The tested complexes exhibited an anti-proliferative effect, this effect was more effective compared to EPS alone. This increase of the antiproliferative properties was explained by a change in conformation of EPS complexes due to their polyelectrolyte nature that was induced by complexation. Alterations of both growth factor-receptor signaling, and transmembrane protein interactions could be the principal cause of the antiproliferative effect. These results are very promising and reveal that EPS can be coupled to scandium for improving its biological effects and also suggesting that no major structural modification

Background: Exopolysaccharide (EPS) derivatives, produced by Alteromonas infernus bacterium, showed anti-metastatic properties. They may represent a new class of ligands to be combined with theranostic radionuclides, such as 47Sc/44Sc. The goal of this work was to investigate the feasibility of such coupling. (2) Methods: EPSs, as well as heparin used as a drug reference, were characterized in terms of molar mass and dispersity using Asymmetrical Flow Field-Flow Fractionation coupled to Multi-Angle Light Scattering (AF4-MALS). The intrinsic viscosity of EPSs at different ionic strengths were measured in order to establish the conformation. To determine the stability constants of Sc with EPS and heparin, a Free-ion selective radiotracer extraction (FISRE) method has been used. (3) Results: AF4-MALS showed that radical depolymerization produces monodisperse EPSs, suitable for therapeutic use. EPS conformation exhibited a lower hydrodynamic volume for the highest ionic strengths. The resulting random-coiled conformation could affect the complexation with metal for high concentration. The LogK of Sc-EPS complexes have been determined and showing that they are comparable to the Sc-Hep. (4) Conclusions: EPSs are very promising to be coupled with the theranostic pair of scandium for Nuclear Medicine.

Theranostic agents based on photo-dynamic therapy exhibited the properties of the noninvasive feature, spatial-temporal control and be free of drug resistance. Herein, based on the principle of “More is Less”, a multifunctional nanoprobe for selective lighting-up of fungi and targeted anti-microbes was designed and achieved. The introducing of the hydroxyl groups and alkaline diethylamino moiety facilitate the probe with well aggregation-induced emission feature, good selectivity towards fungi and acid responsiveness. This probe could only light-up fungi with bright fluorescence, and exhibited diversity anti-microbe behavior towards different microbes. Moreover, the in vitro and in vivo eradication of the supergerm of methicillin resistant staphylococcus aureus was achieved by the treatment of the probe. Confidently, this well-designed nanoprobe is anticipated to have great potential in infective theranostic applications in clinic. © 2021 Elsevier Ltd

[EN]An important motivation for the use of nanomaterials and nanoarchitectures in cancer therapy emanates from the widespread emergence of drug resistance. Although doxorubicin (DOX) induces cell cycle arrest and DNA damage by suppressing topoisomerase activity, resistance to DOX has severely restricted its anti-cancer potential. Hyaluronic acid (HA) has been extensively utilized for synthesizing nanoparticles as it interacts with CD44 expressed on the surface of cancer cells. Cancer cells can take up HA-modified nanoparticles through receptor mediated endocytosis. Various types of nanostructures such as carbon nanomaterials, lipid nanoparticles and polymeric nanocarriers have been modified with HA to enhance the delivery of DOX to cancer cells. Hyaluronic acid-based advanced materials provide a platform for the co-delivery of genes and drugs along with DOX to enhance the efficacy of anti-cancer therapy and overcome chemoresistance. In the present review, the potential methods and application of HA-modified nanostructures for DOX delivery in anti-cancer therapy are discussed.

Bacterial biofilms are a huge burden on our healthcare systems worldwide. The lack of specificity in diagnostic and treatment possibilities result in difficult-to-treat and persistent infections. The aim of this in vitro study was to investigate if microbubbles targeted specifically to bacteria in biofilms could be used both for diagnosis as well for sonobactericide treatment and demonstrate their theranostic potential for biofilm infection management. The antibiotic vancomycin was chemically coupled to the lipid shell of microbubbles and validated using mass spectrometry and high-axial resolution 4Pi confocal microscopy. Theranostic proof-of-principle was investigated by demonstrating the specific binding of vancomycin-decorated microbubbles (vMB) to statically and flow grown Staphylococcus aureus (S. aureus) biofilms under increasing shear stress flow conditions (0–12 dyn/cm2), as well as confirmation of microbubble oscillation and biofilm disruption upon ultrasound exposure (2 MHz, 250 kPa, and 5,000 or 10,000 cycles) during flow shear stress of 5 dyn/cm2 using time-lapse confocal microscopy combined with the Brandaris 128 ultra-high-speed camera. Vancomycin was successfully incorporated into the microbubble lipid shell. vMB bound significantly more often than control microbubbles to biofilms, also in the presence of free vancomycin (up to 1000 µg/mL) and remained bound under increasing shear stress flow conditions (up to 12 dyn/cm2). Upon ultrasound insonification biofilm area was reduced of up to 28%, as confirmed by confocal microscopy. Our results confirm the successful production of vMB and support their potential as a new theranostic tool for S. aureus biofilm infections by allowing for specific bacterial detection and biofilm disruption., ImPhys/Medical Imaging

The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.

Presented are the results of 99mTc and 101Tc production via neutron irradiation of natural isotopic molybdenum (Mo) with epithermal/resonance neutrons. Neutrons were produced using a deuterium-deuterium (D-D) neutron generator with an output of 2 × 1010 n/s. The separation of Tc from an irradiated source of bulk, low-specific activity (LSA) Mo on activated carbon (AC) was demonstrated. The yields of 99mTc and 101Tc, together with their potential use in medical single-photon emission computed tomography (SPECT) procedures, have been evaluated from the perspective of commercial production, with a patient dose consisting of 740 MBq (20 mCi) of 99mTc. The number of neutron generators to meet the annual 40,000,000 world-wide procedures is estimated for each imaging modality: 99mTc versus 101Tc, D-D versus deuterium-tritium (D-T) neu-tron generator system outputs, and whether or not natural molybdenum or enriched targets are used for production. The financial implications for neutron generator production of these isotopes is also presented. The use of 101Tc as a diagnostic, therapeutic, and/or theranostic isotope for use in medical applications is proposed and compared to known commercial nuclear diagnostic and therapeutic isotopes.

Conjugated polymer nanoparticles (CPNs) have emerged as advanced polymeric nanoplatforms in biomedical applications by virtue of extraordinary properties including high fluorescence brightness, large absorption coefficients of one and two-photons, and excellent photostability and colloidal stability in water and physiological medium. In addition, low cytotoxicity, easy functionalization, and the ability to modify CPN photochemical properties by the incorporation of dopants, convert them into excellent theranostic agents with multifunctionality for imaging and treatment. In this work, CPNs were designed and synthesized by incorporating a metal oxide magnetic core (Fe3O4 and NiFe2O4 nanoparticles, 5 nm) into their matrix during the nanoprecipitation method. This modification allowed the in vivo monitoring of nanoparticles in animal models using magnetic resonance imaging (MRI) and intravital fluorescence, techniques widely used for intracranial tumors evaluation. The modified CPNs were assessed in vivo in glioblastoma (GBM) bearing mice, both heterotopic and orthotopic developed models. Biodistribution studies were performed with MRI acquisitions and fluorescence images up to 24 h after the i.v. nanoparticles administration. The resulting IONP-doped CPNs were biocompatible in GBM tumor cells in vitro with an excellent cell incorporation depending on nanoparticle concentration exposure. IONP-doped CPNs were detected in tumor and excretory organs of the heterotopic GBM model after i.v. and i.t. injection. However, in the orthotopic GBM model, the size of the nanoparticles is probably hindering a higher effect on intratumorally T2-weighted images (T2WI) signals and T2 values. The photodynamic therapy (PDT)—cytotoxicity of CPNs was not either affected by the IONPs incorporation into the nanoparticles.

Nanoscale coordination polymers (NCPs) have fascinated researchers over the last years. Their intrinsic theranostic properties of metal ions and organic ligands, the encapsulation of several drugs/biomolecules with excellent yields and the surface functionalisation, enhancing their biocompatibility and targeting, have remarkably impacted in prospective drug delivery alternatives in medicine. Moreover, the properties and characteristics of these nanoparticles (NPs) can be fine-tuned thanks to the synthetic flexibility of coordination chemistry. For all these reasons, the number of examples published has grown exponentially over the last years, embracing different disciplines such as molecular electronics, sensors or nanomedicine, among others. Specifically, significant advances in antitumoural applications are reported, one of the areas where this novel family of NPs has experienced a considerable advance. NCPs have accomplished a high sophistication degree and efficiency as theranostic nanoplatforms (i.e., drug delivery carriers and bioimaging probes) with long residence time in the bloodstream, targeting capacities and remarkable cellular internalisation. In this review, an introduction emphasizing the advantages of NPs for cancer treatment is included. Later on, the most representative examples of NCPs for antitumoural applications are described grouped into six mean representative areas: i) encapsulation approaches, ii) stimuli-responsive NCPs, iii) metal chemotherapy, iv) photodynamic therapy (PDT), v) unconventional therapeutic approaches and vi) theranostics. Particular emphasis is given to understand the encapsulation/release properties of these particles at the nanoscale and their interaction with biological environments, highlighting any limitation and challenges that these systems are facing from a clinical translation perspective and envisioning possible future trends and areas that will deserve further attention for the following years.

L'arrivée de la nanotechnologie a révolutionné les sciences fondamentales et applicatives. En biomédecine, les concepts diagnostiques et thérapeutiques qui étaient auparavant de la science-fiction prennent graduellement vie sous forme de nanoparticules sophistiquées - mettant en œuvre la détection et le traitement des maladies. Les nanoparticules photoluminescentes, qui répondent au stimulus optique en émettant de la lumière utilisée pour l'imagerie, la détection et la thérapie, sont des agents théranostiques prometteurs, intégrant ensemble le diagnostic et la thérapie. Les nanoparticules préférées sont celles qui fonctionnent sous de longueurs d'onde proche infrarouge (NIR), qui transpercent plus profondément les tissus et ne se limitent pas à une application superficielle seule. Parmi celles-ci, les nanoparticules dopées aux terres rares, ou RENP, sous excitation NIR peuvent émettre à travers les gammes spectrales UV, visible et NIR. Grâce à la conversion ascendante des photons, les RENP ajoutent de multiples photons dans le proche infrarouge et émettent une lumière d'une énergie suffisamment élevée pour stimuler les processus thérapeutiques. De plus, l'excitation NIR est émise sous forme de lumière de longueurs d'onde encore plus grandes, ce qui est parfait pour l'imagerie et la détection des indices environnementaux, comme la température. En fait, les RENP sont d'excellents nanothermomètres, explorés pour la détection précoce des maladies et l'exécution contrôlée des thérapies basées sur la chaleur. Cette thèse explore les RENP en tant que futures nanomédicaments théranostiques, en se concentrant sur les RENP qui émettent à travers une large gamme spectrale, UV-NIR. Des propriétés photophysiques fondamentales de différents RENP sont signalées, nécessaires pour brosser un tableau réaliste du potentiel et des pièges de ces nanostructures. En outre, les premiers RENP du genre en tant que nanothermomètres fonctionnant au-delà de 1500 nm de longueurs d'onde sont intr

A set of BODIPY‐carboranyl dyads synthesized by a Sonogashira cross‐coupling reaction, where different C‐substituted ortho‐ and meta‐carboranyl fragments have been linked to a BODIPY fluorophore is described. Chemical, photophysical and physicochemical analyses are presented, including NMR and SXRD experiments, optical absorption/emission studies and log P measurements. These studies, supported by DFT computations (M06‐2X/6‐31G**) provide an explanation to the largely divergent cell income that these fluorescent carboranyl‐based fluorophores display, for which a structural or physicochemical explanation remains elusive. By studying the cell uptake efficiency and subcellular localization for our set of dyads on living HeLa cells, we tracked the origins of these differences to significant variations in their static dipole moments and partition coefficients, which tune their ability to interact with lipophilic microenvironments in cells. Remarkably, m‐carboranyl‐BODIPY derivatives with a higher lipophilicity are much better internalised by cells than their homologous with o‐carborane, suggesting that m‐isomers are potentially better theranostic agents for in vitro bioimaging and boron carriers for BNCT.

With the ongoing research in nuclear medicine new targets can be visualized and used as therapy. With a special focus on the androgen receptor, which is a member of the steroid and nuclear hormone receptor family, the receptor is known as a target for prostate cancer, but also for breast, kidney, colon lung, pancreatic and rectal cancer. All these tumors and other diseases might profit from the detection and the therapy of the androgen receptor and will be discussed in this thesis.*****With the ongoing research in nuclear medicine new targets can be visualized and used as therapy. With a special focus on the androgen receptor, which is a member of the steroid and nuclear hormone receptor family, the receptor is known as a target for prostate cancer, but also for breast, kidney, colon lung, pancreatic and rectal cancer. All these tumors and other diseases might profit from the detection and the therapy of the androgen receptor and will be discussed in this thesis.

Theranostic systems are materials or processes that combine modalities of diagnostic imaging with the delivery of therapeutics. The information obtained from theranostic drug-delivery systems can be used to make decisions in real time in efforts to optimize the treatment. This combination of therapy and diagnostics in a single treatment is a viable method for improving drug efficacy, patient safety, and therapeutic outcomes. The theranostic delivery of carbon monoxide (CO) as a chemotherapeutic and silver (Ag+) as an antibacterial agent is discussed in detail in the following chapters.The gaseous signaling molecule carbon monoxide has been recently recognized for its wide range of physiological activity as well as its antineoplastic properties. Endogenously produced CO directly regulates heme protein activity and indirectly modulates a variety of biochemical processes. Exogenous delivery of CO is also a viable strategy for influencing cellular biochemical responses in efforts to elicit desired salutary therapeutic effects. However, the main technical challenge is the delivery of this noxious and potentially hazardous gas in a controlled and dependable manner. Several elegant strategies have been designed and implemented for the delivery of this gaseous signaling molecule to cells, including photo-triggered CO releasing systems (molecules, materials, carriers). Light can be used as a benign remote trigger for the on-demand release of CO from photoactivatable CO-releasing systems (photoCORs). However, the delivery of CO to light inaccessible cavities/tissues with spatiotemporal control is a considerable challenge. The delivery of CO to remote parts of the body through the use of an optical fiber-based CO-releasing device is discussed in Chapter 2.I. The CO-releasing polymeric material described in this chapter can be used as a solid-state source of CO triggered through external light illumination. In addition, this material exhibits a color change upon CO release, ind

One of the holy grails in cancer therapy is to simultaneously image and deliver drugs to the tumor site. The first part of the thesis has developed new ideas in cancer theranostics and the second part is about the development of a novel contrast agent for risk-free imaging of the tumor. In the first project of the thesis, I have discussed the development of a liposome-based cargo delivery strategy that can simultaneously monitor alternating magnetic field–induced drug release by observing the change in MRI relaxation parameter R1, and the location and condition of liposomal site (such as tumor) from MRI parameter R2. However, the loading of a contrast agent in liposomes generally results in poor contrast and suffers from various artifacts in in vivo experiments, compared to the use of free contrast agent. Thus, the second project of my work in this part demonstrates the effective filtering of artifacts and contrast enhancement to obtain high quality sensitive imaging of the tumor site in a mouse model using paramagnetic liposomes, a novel pulsing sequence in active-feedback MRI, and robust data analysis. The second part of my work is about using a self-replicating viral-RNA molecule derived from Nodamura, an insect virus, to express and amplify ferritin, leading to increased iron content of the cells in the form of ferrihydrite that acts as a novel contrast agent. In summary, my thesis is about the development of cancer theranostics and a novel contrast agent. In the last part of the thesis, I have reviewed the current development of rapidly growing state of the art magnetic resonance cancer theranostics for commonly used polymer-based nanovehicles.

Imaging plays a pivotal role in the diagnostic and prognostic assessment of cardiovascular diseases. During the past two decades, there has been an expansion of the available imaging techniques, some of which are now part of routine clinical practice. Cardiovascular imaging of atherosclerosis is a useful instrument, and it can corroborate and expand pathophysiological evidence on cardiovascular disease, providing proof of concept for medical therapy and can predict its responsiveness, and it may be able to be used as surrogate endpoints for clinical trials. Theranostics is an emerging therapy that combines imaging and therapeutic functions, using imaging-based therapeutic delivery systems. Theranostics could partially overcome current imaging limitations and translate experimental evidence and large-scale trials assessing clinical endpoints, rationalising cardiovascular drug development and paving the way to personalised medicine. The medical community cannot overlook the use of cardiovascular imaging as a complementary and supportive adjunct to trials investigating clinical endpoints, which remain the mainstay for investigating the efficacy and safety of cardiovascular pharmacotherapy.

Block copolymer nanoparticles (NPs) have gained great attention among researcher for various medical application mainly due to their extraordinary optical, chemical, and biological properties. The current thesis presents design of multifunctional polymeric NPs for imaging and drug delivery system (DDS) with an in-vitro study of their participation in drug release and cell viability. The NPs were synthesized using reversible addition chain fragmentation transfer (RAFT)-mediated emulsion polymerization via polymerization induce self-assembly (PISA) approach. The environment-friendly emulsion polymerization process of n-buytl acrylate (n-BA) in water is highly efficient. The process produced uniform NPs which would have control over the particle size and molecular weight of the compound. Herein we report a novel simultaneous encapsulation of camptothecin (CPT) and Nile red (NR) into poly(ethylene glycol) methyl ether methacrylate-co-N-hydroxyethyl acrylamide-b-poly n-buytlacrylate (PEGA-co-HEAA)-b-P(n-BA) during the particles formation with a small particle size of 66 nm, high conversion ~80% and encapsulation efficiency of ~50%. The In vitro drug release of the CPT from the NPs exhibited an initial burst (70-80%) within 6h. cell viability was evaluated for the NPs against RAW 264.7 cell line, which indicated the designed NPs are biocompatible and not toxic.

Taking advantage of the radiation properties of 99mTc and 186/188Re and the photophysical characteristics of the {M(CO)3}+ moiety (M = Re), we developed a multifunctional silica platform with the theranostic pair 99mTc/Re with high potential for (nano)medical applications. Starting with a general screening to evaluate the most suitable mesoporous silica construct and the development of appropriate chelate systems, multifunctional mesoporous silica microparticles (SBA-15) were synthesized. These particles act as a model towards the synthesis of the corresponding nanoconstructs. The particles can be modified at the external surface with a targeting function and labeled with the {M(CO)3}+ moiety (M = 99mTc, Re) at the pore surface. Thus, a silica platform is realized, whose bioprofile is not altered by the loaded modalities. The described synthetic procedures can be applied to establish a target-specific theranostic nanoplatform, which enables the combination of fluorescence and radio imaging, with the possibility of radio- and chemotherapy.

Molecular imaging is becoming essential for precision targeted radiation therapy, yet progress is hindered from a lack of integrated imaging and treatment systems. We report the development of a prototype positron emission tomography (PET) scanner integrated into a commercial cone beam computed tomography (CBCT) based small animal irradiation system for molecular-image-guided, targeted external beam radiation therapy. The PET component consists of two rotating Hamamatsu time-of-flight PET modules positioned with a bore diameter of 101.6 mm and a radial field-of-view of 53.1 mm. The measured energy resolution after linearity correction at 511 KeV was 12.9% and the timing resolution was 283.6 ps. The measured spatial resolutions at the field-of-view center and 5 mm off the radial center were 2.6 mm × 2.6 mm × 1.6 mm and 2.6 mm × 2.6 mm × 2.7 mm respectively. 18F-Fluorodeoxyglucose-based PET imaging of a NEMA NU 4-2008 phantom resolved cylindrical volumes with diameters as small as 3 mm. To validate the system in-vivo, we performed 64Cu-DOTA-M5A PET and computed tomography (CT) imaging of carcinoembryonic antigen (CEA)-positive colorectal cancer in athymic nude mice and compared the results with a commercially available Siemens Inveon PET/CT system. The prototype PET system performed comparably to the Siemens system for identifying the location, size, and shape of tumors. Regions of heterogeneous 64Cu-DOTA-M5A uptake were observed. Using 64Cu-DOTA-M5A PET and CT images, a Monte Carlo-based radiation treatment plan was created to escalate the dose to the 64Cu-DOTA-M5A-based, highly active, biological target volume while largely sparing the normal tissue. Results demonstrate the feasibility of molecular-image-guided treatment plans using the prototype theranostic system.

Bone defects due to different diseases and trauma represent a significant health problem. For the follow up on the healing process a sensor which measures the bone mineral density has been developed in the firm of a sensitive split-ring microwave resonator. However, it is not only important to follow up of the healing process but also to find ways of improving the healing, where one way exploited here is to use an externally applied low frequency magnetic field to increase the cell proliferation in the fractured hones. This combines high frequency (microwave) technique with the low frequency (magnetic field) creating a theranostic instrument for clinical and hotneca re applications.

Background: Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions. Methods: Patients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo biodistribution and lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1 till H144 after IV injection of 187 MBq of 111In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dose when using 90Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between 370 MBq (Arm A) and 1110 MBq (Arm B) of 90Y-OTSA-101 for radionuclide therapy. Results: From January 2012 to June 2015, 20 pts. (median age 43 years [21–67]) with advanced SS were enrolled. Even though 111In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy for each patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake to proceed to treatment with 90Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were not randomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, which were more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patients lasting up to 21 weeks for 1 patient. Conclusions: Radioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least one lesion with 111In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 M

The idea of multifunctional nanomedicine that enters the human body to diagnose and treat disease without major surgery is a long-standing dream of nanomaterials scientists. Nanomaterials show incredible properties that are not found in bulk materials, but achieving multi-functionality on a single material remains challenging. Integrating several types of materials at the nano-scale is critical to the success of multifunctional nanomedicine device. Here, we describe the advantages of silica nanoparticles as a tool for multifunctional nano-devices. Silica nanoparticles have been intensively studied in drug delivery due to their biocompatibility, degradability, tunable morphology, and ease of modification. Moreover, silica nanoparticles can be integrated with other materials to obtain more features and achieve theranostic capabilities and multimodality for imaging applications. In this review, we will first compare the properties of silica nanoparticles with other well-known nanomaterials for bio-applications and describe typical routes to synthesize and integrate silica nanoparticles. We will then highlight theranostic and multimodal imaging application that use silica-based nanoparticles with a particular interest in real-time monitoring of therapeutic molecules. Finally, we will present the challenges and perspective on future work with silica-based nanoparticles in medicine.

The enhanced permeability and retention (EPR) effect increases tumor accumulation of liposomal chemotherapy and should, in theory, increase anticancer effects and lower toxicity. Unfortunately, liposomal chemotherapy has generally not met the expected potential, perhaps because the EPR effect is not ubiquitous. PET imaging using radiolabeled liposomes can identify cancers positive for the EPR effect. In the current study, we show in clinical canine cancer patients that repeated imaging with radiolabeled liposomes ( 64Cu-liposome) induces the accelerated blood clearance (ABC) phenomenon. This was observed even with very long intervals between PEGylated liposome injections, which contradict previous reporting in experimental animal models. The induction of ABC may be devastating for the theranostic use of liposomal imaging, as this could vaccinate patients against therapeutic efficacy. To investigate and solve this important problem, an additional study part was designed in which rats were subjected to repeated liposomal administrations, including stealth 64Cu-liposome PET imaging and Caelyx chemotherapy. Most importantly, it was found that, by increasing the lipid dose at the first injection or by supplying a small predose before the second 64Cu-liposome injection, ABC could be prevented. Importantly, signs of liposome tracer breakdown with subsequent renal excretion were observed. These findings highlight the importance of the ABC phenomenon for liposomal predictive imaging in a clinically relevant setting and show that carefully planned application is central to avoid potential detrimental effects on patient benefit.

Prostate cancer (PC) includes several phenotypes, from indolent to highly aggressive cancer. Actual diagnostic and prognostic tools have several limitations, and there is a need for new biomarkers to stratify patients and assign them optimal therapies by taking into account potential genetic and epigenetic differences. MicroRNAs (miRNAs) are small sequences of non-coding RNA regulating specific genes involved in the onset and development of PC. Stable miRNAs have been found in biofluids, such as serum and plasma; thus, the measurement of PC-associated miRNAs is emerging as a non-invasive tool for PC detection and monitoring. In this study, we conduct an in-depth literature review focusing on miRNAs that may contribute to the diagnosis and prognosis of PC. The role of miRNAs as a potential theranostic tool in PC is discussed. Using a meta-analysis approach, we found a group of 29 miRNAs with diagnostic properties and a group of seven miRNAs with prognostic properties, which were found already expressed in both biofluids and PC tissues. We tested the two miRNA groups on The Cancer Genome Atlas dataset of PC tissue samples with a machine-learning approach. Our results suggest that these 29 miRNAs should be considered as potential panel of biomarkers for the diagnosis of PC, both as in vivo non-invasive test and ex vivo confirmation test.

The present study successfully developed orally deliverable multimodular zinc (Zn) iron oxide (Fe3O4)-saturated bovine lactoferrin (bLf)-loaded polymeric nanocapsules (NCs), and evaluated their theranostic potential (antitumor efficacy, magnetophotothermal efficacy and imaging capability) in an in vivo human xenograft CpG-island methylator phenotype (CIMP)-1(+)/CIMP2(-)/chromosome instability-positive colonic adenocarcinoma (Caco2) and claudin-low, triple-negative (ER(-)/PR(-)/HER2(-); MDA-MB-231) breast cancer model. Mice fed orally on the Zn-Fe-bLf NC diet showed downregulation in tumor volume and complete regression in tumor volume after 45 days of feeding. In human xenograft colon cancer, vehicle-control NC diet-group (n=5) mice showed a tumor volume of 52.28±11.55 mm(3), and Zn-Fe-bLf NC diet (n=5)-treated mice had a tumor-volume of 0.10±0.073 mm(3). In the human xenograft breast cancer model, Zn-Fe-bLf NC diet (n=5)-treated mice showed a tumor volume of 0.051±0.062 mm(3) within 40 days of feeding. Live mouse imaging conducted by near-infrared fluorescence imaging of Zn-Fe-bLf NCs showed tumor site-specific localization and regression of colon and breast tumor volume. Ex vivo fluorescence-imaging analysis of the vital organs of mice exhibited sparse localization patterns of Zn-Fe-bLf NCs and also confirmed tumor-specific selective localization patterns of Zn-Fe-bLf NCs. Dual imaging using magnetic resonance imaging and computerized tomography scans revealed an unprecedented theranostic ability of the Zn-Fe-bLf NCs. These observations warrant consideration of multimodular Zn-Fe-bLf NCs for real-time cancer imaging and simultaneous cancer-targeted therapy.

Herein we report a theranostic system based on iron oxide-gadolinium nanoparticles coated by chitosan as a dual contrast agent for magnetic resonance imaging and controlled delivery application. Iron oxide nanoparticles were prepared by reduction of iron (III) chloride followed by surface modification using arenediazonium tosylate and diethylenetriaminepentaacetic acid for Gd(III) complexation. Nanoparticles were loaded with the anticancer drug doxorubicin and coated by low molecular weight chitosan to improve stability in solution and control the release of the drug. Dynamic light scattering, z-potential, thermogravimetric analysis, attenuated total refraction infrared spectroscopy and magnetic hysteresis curves reveal the success of surface modification and coating process. The amount of Gd(III) complexed and doxorubicin loaded were assessed by UV-Vis. Release studies were carried out in simulated physiological conditions. Results indicate that the obtained iron oxide-Gd(III) nanoparticles coated by chitosan are stable up to one month in physiological conditions and magnetic response is slightly decreased. The MRI analysis, doxorubicin high encapsulation efficiency and sustained release trend suggests that the presented system represents an interesting platform for the development of future theranostic agents.

The access to no-carrier-added 197(m)Hg using proton irradiation of gold targets and subsequent product separation was recently reported. One of the limiting factors of the large-scale production of this theranostic radionuclide is rather low yield of the 197Au(p,n)197(m)Hg reaction. In contrast, significantly larger cross-sections have been reported for 197Au(d,2n) reaction. In spite of somewhat larger linear energy transfer of deuterons in gold, the latter reaction seems to result in larger achievable activity of 197(m)Hg. We have, therefore, explored its potential for the 197(m)Hg production in a pilot experiment.

The no-carrier-added (NCA) radionuclide 197(m)Hg is accessible in adequate quantity and quality for radiopharmaceutical research through the proton irradiation of gold using a cyclotron.1 The interest in this mercury isotope was prompted primarily by the decay characteristics of both nuclear isomers, like convenient half-life (197mHg = 23.8 h, 197Hg = 64.14 h), low energy gamma radiations useful for diagnosis (197mHg = 133.98 keV, 33.5% , 197Hg = 77.4 keV, 18.7%) and numerous Auger- and conversion electrons with high potential for cancer therapy. Additionally, the unique chemical properties of mercury allow for the development of promising radiolabeling tools and new radiopharmaceuticals. In addition to the typical metal properties to form coordination compounds with sulfur, nitrogen and oxygen containing ligands, mercury has the special ability to build water stable carbon-metal bonds. The reactivity of the mercury(II) ions towards sulfur containing ligands, solvomercuration of alkenes and electrophilic aromatic substitutions were investigated to prepare a stable labeling unit at NCA level with 197(m)Hg. While both the mercury thiolate complexes and the products of solvomercuration exhibited low stability in the presence of competing thiol ligands and are therefore unsuitable for radiopharmaceutical applications, symmetric diarylmercury compounds showed high stability against competing ligands. The development and application of a prelabeling tool based on a bis-benzoyl-mercury derivative as succinimidyl ester will be reported.

Despite an improved understanding of its pathophysiology and a wide range of new treatments, cardiovascular disease (CVD) remains a serious public health issue and the number one cause of mortality in the United States. Conditions that promote chronic systemic inflammation, such as obesity, cancer, and autoimmune and infectious diseases, are now known to play an important role in promoting CVD by inducing the expression of endothelial adhesion molecules and chemokines; these in turn promote leukocyte adherence and infiltration, which initiates and spurs the progression of CVD. In response to this new understanding, researchers are evaluating the potential cardiovascular benefits of new-generation therapies based on endogenous molecules with anti-inflammatory properties. Similarly, targeted approaches that leverage the phenotypic differences between non-inflamed and inflamed endothelia have the potential to selectively deliver therapeutics and decrease the morbidity and mortality of CVD patients. In this review, we discuss the role of inflammation in CVD and explore the therapeutic potential of targeting inflamed vasculature through conventional and biomimetic approaches.

Perimidines are extensively studied for their different therapeutic properties, including antiulcer, antifungal, antimicrobial, immunosuppressive and anticancer activities. Moreover, their heterocyclic structure embodies the naphthalene moiety, exploited in bio-imaging and biomolecules staining due to its high fluorescence. In this work we present the spectroscopic characterization of a family of perimidine derivatives, in order to obtain information potentially useful for the design of compounds combining biological activity and detectable fluorescence in physiological environment.

Gold nanocages (AuNCs) have been shown to be a useful tool for harnessing imaging and hyperthermia therapy of cancer, thanks to their unique optical properties, low toxicity, and facile surface functionalization. Herein, we use AuNCs for selective targeting of prostate cancer cells (PC3) via specific interaction between neuropeptide Y (NPY) receptor and three different NPY analogs conjugated to AuNCs. Localized surface plasmon resonance band of the nanoconjugates was set around 800 nm, which is appropriate for in vivo applications. Long-term stability of nanoconjugates in different media was confirmed by UV-vis and DLS studies. Active NPY receptor targeting was observed by confocal microscopy showing time-dependent AuNCs cellular uptake. Activation of ERK1/2 pathway was evaluated by Western blot to confirm the receptor-mediated specific interaction with PC3. Cellular uptake kinetics were compared as a function of peptide structure. Cytotoxicity of nanoconjugates was evaluated by MTS and Annexin V assays, confirming their safety within the concentration range explored. Hyperthermia studies were carried out irradiating the cells, previously incubated with AuNCs, with a pulsed laser at 800 nm wavelength, showing a heating enhancement ranging from 6 to 35 °C above the culture temperature dependent on the irradiation power (between 1.6 and 12.7 W/cm2). Only cells treated with AuNCs underwent morphological alterations in the cytoskeleton structure upon laser irradiation, leading to membrane blebbing and loss of microvilli associated with cell migration. This effect is promising in view of possible inhibition of proliferation and invasion of cancer cells. In summary, our Au-peptide NCs proved to be an efficient theranostic nanosystem for targeted detection and activatable killing of prostate cancer cells.

The objective of this study was to evaluate the potentialof PEGylated 64Cu-liposomes in clinical diagnosticpositron emission tomography (PET) imaging andPEGylated 177Lu-liposomes in internal tumor radiotherapythrough in vivo characterization and dosimetric analysis in ahuman xenograft mouse model. Liposomes with 5 and 10 mol% PEG were characterizedwith respect to size, charge, and 64Cu- and 177Lu-loadingefficiency. The tumor imaging potential of 64Cu-loadedliposomes was evaluated in terms of in vivo biodistribution,tumor accumulation and tumor-to-muscle (T/M) ratios, usingPET imaging. The potential of PEGylated liposomes for diagnosticand therapeutic applications was further evaluatedthrough dosimetry analysis using OLINDA/EXM software.The 64Cu-liposomes were used as biological surrogates toestimate the organ and tumor kinetics of 177Lu-liposomes.High remote loading efficiency (>95 %) was obtainedfor both 64Cu and 177Lu radionuclides with PEGylated liposomes,and essentially no leakage of the encapsulated radionuclidewas observed upon storage and after serum incubationfor 24 h at 37 °C. The 10 mol% PEG liposomes showedhigher tumor accumulation (6.2±0.2 %ID/g) than the 5mol% PEG liposomes, as evaluated by PET imaging. Thedosimetry analysis of the 64Cu-liposomes estimated an acceptabletotal effective dose of 3.3·10−2 mSv/MBq for diagnosticimaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic 177Luliposomes. The overall preclinical profile of PEGylated64Cu-liposomes showed high potential as a new PETtheranostic tracer for imaging in humans. Dosimetry resultspredicted that initial administered activity of 200 MBq of64Cu-liposomes should be acceptable in patients. Work is inprogress to validate the utility of PEGylated 64Cu-liposomesin a clinical research programme. The high absorbed tumordose (114 mGy/MBq) estimated for 177Lu-liposomes and thepreliminary dosimetric studies justify further therapeutic anddosimetr

Increasing cell survival in stem cell therapy is an important challenge for the field of regenerative medicine. Here, we report theranostic mesoporous silica nanoparticles that can increase cell survival through both diagnostic and therapeutic approaches. First, the nanoparticle offers ultrasound and MRI signal to guide implantation into the peri-infarct zone and away from the most necrotic tissue. Second, the nanoparticle serves as a slow release reservoir of insulin-like growth factor (IGF)-a protein shown to increase cell survival. Mesenchymal stem cells labeled with these nanoparticles had detection limits near 9000 cells with no cytotoxicity at the 250 µg/mL concentration required for labeling. We also studied the degradation of the nanoparticles and showed that they clear from cells in approximately 3 weeks. The presence of IGF increased cell survival up to 40% (p<0.05) versus unlabeled cells under in vitro serum-free culture conditions.

Dysregulation of microRNAs (miRNAs) is involved in the initiation and progression of several human cancers, including breast cancer (BC), as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. This review presents the state of the art on the role of miRNAs in the diagnosis, prognosis, and therapy of BC. Based on the results obtained in the last decade, some miRNAs are emerging as biomarkers of BC for diagnosis (i.e., miR-9, miR-10b, and miR-17-5p), prognosis (i.e., miR-148a and miR-335), and prediction of therapeutic outcomes (i.e., miR-30c, miR-187, and miR-339-5p) and have important roles in the control of BC hallmark functions such as invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability. Other miRNAs are of interest as new, easily accessible, affordable, non-invasive tools for the personalized management of patients with BC because they are circulating in body fluids (e.g., miR-155 and miR-210). In particular, circulating multiple miRNA profiles are showing better diagnostic and prognostic performance as well as better sensitivity than individual miRNAs in BC. New miRNA-based drugs are also promising therapy for BC (e.g., miR-9, miR-21, miR34a, miR145, and miR150), and other miRNAs are showing a fundamental role in modulation of the response to other non-miRNA treatments, being able to increase their efficacy (e.g., miR-21, miR34a, miR195, miR200c, and miR203 in combination with chemotherapy).

A major drawback with current cancer therapy is the prevalence of unrequired dose-limiting toxicity to non-cancerous tissues and organs, which is further compounded by a limited ability to rapidly and easily monitor drug delivery, pharmacodynamics and therapeutic response. In this report, the design and characterization of novel multifunctional "theranostic" nanoparticles (TNPs) is described for enzyme-specific drug activation at tumor sites and simultaneous in vivo magnetic resonance imaging (MRI) of drug delivery. TNPs are synthesized by conjugation of FDA-approved iron oxide nanoparticles ferumoxytol to an MMP-activatable peptide conjugate of azademethylcolchicine (ICT), creating CLIO-ICTs (TNPs). Significant cell death is observed in TNP-treated MMP-14 positive MMTV-PyMT breast cancer cells in vitro, but not MMP-14 negative fibroblasts or cells treated with ferumoxytol alone. Intravenous administration of TNPs to MMTV-PyMT tumor-bearing mice and subsequent MRI demonstrates significant tumor selective accumulation of the TNP, an observation confirmed by histopathology. Treatment with CLIO-ICTs induces a significant antitumor effect and tumor necrosis, a response not observed with ferumoxytol. Furthermore, no toxicity or cell death is observed in normal tissues following treatment with CLIO-ICTs, ICT, or ferumoxytol. These findings demonstrate proof of concept for a new nanotemplate that integrates tumor specificity, drug delivery and in vivo imaging into a single TNP entity through attachment of enzyme-activated prodrugs onto magnetic nanoparticles. This novel approach holds the potential to significantly improve targeted cancer therapies, and ultimately enable personalized therapy regimens.

Gemcitabine is a highly potent chemotherapeutic nucleoside agent used in the treatment of several cancers and solid tumors. However, it is therapeutically limitated because of toxicity to normal cells and its rapid intracellular deamination by cytidine deaminase into the inactive uracil derivative. Modification at the 4-(N) position of gemcitabine's exocyclic amine to an -amide functionality is a well reported prodrug strategy which has been that confers a resistance to intracellular deamination while also altering pharmacokinetics of the parent drug. Coupling of gemcitabine to carboxylic acids with varying terminal moieties afforded the 4-N-alkanoylgemcitabines whereas reaction of 4-N-tosylgemcitabine with the corresponding alkyl amines gave the 4-N-alkylgemcitabines. The 4-N-alkanoyl and 4-N-alkyl gemcitabine analogues with a terminal hydroxyl group on the 4-N-alkanoyl or 4-N-alkyl chain were efficiently fluorinated either with diethylaminosulfur trifluoride or under conditions that are compatible with the synthetic protocols for 18F labeling, such as displacement of the corresponding mesylate with KF/Kryptofix 2.2.2. The 4-N-alkanoylgemcitabine analogues displayed potent cytostatic activities against murine and human tumor cell lines with 50% inhibitory concentration (IC50) values in the range of low nM, whereas cytotoxicity of the 4-N-alkylgemcitabine derivatives were in the low to modest µM range. The cytostatic activity of the 4-N-alkanoylgemcitabines was reduced by several orders of magnitude in the 2'-deoxycytidine kinase (dCK)-deficient CEM/dCK- cell line while the 4-N-alkylgemcitabines were only lowered by 2-5 times. None of the 4-N-modified gemcitabines were found to be substrates for cytosolic dCK, however all were found to inhibit DNA synthesis. As such, the 4-N-alkanoyl gemcitabine derivatives likely need to be converted to gemcitabine prior to achieving their significant cytostatic potential, whereas the 4-N-alkylgemcitabines reach their modest activi

Fabrication of multifunctional ultrasound contrast agents (UCAs) has been recently addressed by several research groups. A versatile strategy for the synthesis of UCA precursors in the form of biodegradable vesicles with a biocompatible crosslinked polymer shell is described. Upon ultrasound irradiation, acoustic droplet vaporization transforms such particles into microbubbles behaving as UCAs. This proof of concept entails the features of a potential theranostic microdevice., QC 20131211, 3 MiCRON EU FP7

Wound healing involves a complex series of biochemical events and has traditionally been managed with 'low tech' dressings and bandages. The concept that diagnostic and theranostic sensors can complement wound management is rapidly growing in popularity as there is tremendous potential to apply this technology to both acute and chronic wounds. Benefits in sensing the wound environment include reduction of hospitalization time, prevention of amputations and better understanding of the processes which impair healing. This review discusses the state-of-the-art in detection of markers associated with wound healing and infection, utilizing devices imbedded within dressings or as point-of-care techniques to allow for continual or rapid wound assessment and monitoring. Approaches include using biological or chemical sensors of wound exudates and volatiles to directly or indirectly detect bacteria, monitor pH, temperature, oxygen and enzymes. Spectroscopic and imaging techniques are also reviewed as advanced wound monitoring techniques. The review concludes with a discussion of the limitations of and future directions for this field.

The synthesis and characterization of gold nanoparticles (AuNPs 20. nm sized) modified with k-casein derived peptides in order to monitor the peptide effect as bacterial adhesion inhibitor, thanks to the carrier/concentrator effect of the AuNPs is here presented. Some aspects related to the stability of AuNP/peptide conjugates for a potential application in the design of an electrochemical biosensor for pathogen bacteria detection are also discussed. This peptide based nanoparticle assay takes advantage of the dual character of the AuNPs: as carrier of the biorecognition molecule and also as electrocatalytic label, allowing the evaluation of the pathogen bacteria-peptide interaction in a simple and rapid way through the chronoamperometric monitoring of the hydrogen evolution reaction on screen-printed carbon electrodes. The developed proof of concept theranostic system may open the way to therapeutic and biosensing applications with interest for various fields. © 2012 Elsevier B.V.