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Nanoparticles capable of mimicking natural tissues represent a major technological advancement in regenerative medicine. In this pilot study, the development of a new nanohybrid composed of titanate nanoribbons to mimic the extracellular matrix is reported. During the first phase, nanoribbons were synthesized by hydrothermal treatment. Subsequently, titanate nanoribbons were functionalized by heterobifunctional polyethylene-glycol (PEG) to graft type I collagen on their surface. Biological properties of this new nanobiohybrid such as cytotoxicity to cardiac cells and platelet aggregation ability were evaluated. The so-formed nanobiohybrid permits cellular adhesion and proliferation favoring fine cardiac tissue healing and regeneration.

The association between chemotherapeutic drugs and metal oxide nanoparticles has sparked a rapidly growing interest in cancer nanomedicine. The elaboration of new engineered docetaxel (DTX)-nanocarriers based on titanate nanotubes (TiONts) was reported. The idea was to maintain the drug inside cancer cells and avoid multidrug resistance mechanisms, which often limit drug efficacy by decreasing their intracellular concentrations in tumor cells. HS-PEGn-COOH (PEG: polyethylene glycol, n = 3000, 5000, 10,000) was conjugated, in an organic medium by covalent linkages, on TiONts surface. This study aimed to investigate the influence of different PEG derivatives chain lengths on the TiONts colloidal stability, on the PEGn density and conformation, as well as on the DTX biological activity in a prostate cancer model (human PC-3 prostate adenocarcinoma cells). In vitro tests highlighted significant cytotoxicities of the drug after loading DTX on PEGn-modified TiONts (TiONts-PEGn-DTX). Higher grafting densities for shorter PEGylated chains were most favorable on DTX cytotoxicity by promoting both colloidal stability in biological media and cells internalization. This promising strategy involves a better understanding of nanohybrid engineering, particularly on the PEGylated chain length influence, and can thus become a potent tool in nanomedicine to fight against cancer.

International audience; The quest for small molecules that strongly bind to Gquadruplex-DNA (G4), so-called G4 ligands, has invigorated the G4 research field from its very inception. Massive efforts have been invested to discover or rationally design G4 ligands, evaluate their G4interacting properties in vitro through a series of now widely accepted and routinely implemented assays, and use them as innovative chemical biology tools to interrogate cellular networks that might involve G4s. In sharp contrast, only uncoordinated efforts aimed at developing small molecules that destabilize G4s have been invested to date, even though it is now recognized that such molecular tools would have tremendous application in neurobiology as many genetic and age-related diseases are caused by an overrepresentation of G4s. Herein, we report on our efforts to develop in vitro assays to reliably identify molecules able to destabilize G4s. This workflow comprises the newly designed G4-unfold assay, adapted from the G4-helicase assay implemented with Pif1, as well as a series of biophysical and biochemical techniques classically used to study G4/ligand interactions (CD, UV−vis, PAGE, and FRET-melting), and a qPCR stop assay, adapted from a Taq-based protocol recently used to identify G4s in the genomic DNA of Schizosaccharomyces pombe. This unique, multipronged approach leads to the characterization of a phenylpyrrolocytosine (PhpC)-based G-clamp analog as a prototype of G4disrupting small molecule whose properties are validated through many different and complementary in vitro evaluations.

International audience; The concept of nanomaterials that can be designed and administered into the human body to improve health is of great interest. During the past years there has been an increasing amount of research on the uses of nanomaterials in diverse areas of biomedical research including biological sensing, labelling, imaging, cell separation and therapy. In this chapter, the first evaluation of titanate nanotubes (TiONts) as potential carriers of therapeutic molecules is presented. TiONts with controlled parameters have been developed from a hydrothermal synthesis and their biomedical applications have been explored over the last decade. These nanotubes are elaborated as stable suspensions of nanocarriers by surface chemistry engineering. They can be used as transfection agents for cardiomyocytes and we have shown that TiONts can increase the ionizing effect of radiation therapy in the case of glioblastoma. Furthermore, TiONts' biodistribution has been evaluated by SPECT/CT in male Swiss nude mice and TiONts are quickly cleared. More recently, we have demonstrated that TiONts-docetaxel (DTX) nanohybrids are versatile nanocarriers to limit the systemic toxicity of taxanes and to improve the selectivity of radiotherapy (RT). Our strategy is based on the intraprostatic injection of the TiONts-DTX nanohybrids both in place of brachytherapy and in combination with RT. This is achieved by taking advantage of the TiONts' morphology as well as their radiosensitization effect and by associating them with docetaxel molecules, also recognized for their radiosensitizing potential. We also grafted the surface of TiONts with gold nanoparticles, for a resulting combined radiosensitizing effect. The elaboration of nanohybrid materials, intended for drug delivery systems and based on TiONts coated with chitosan polymer has also been evaluated. Such nanotubes are combined with transresveratrol derivatives for their anti-oxidizing and antitumor effects. All the aspects of a potential toxicity are also considered.

International audience; Nanomaterials have a huge potential in research fields from nanomedicine to medical devices. However, surface modifications of nanoparticles (NPs) and thus of their physicochemical properties failed to predict their biological behavior. This requires investigating the "missing link" at the nano-bio interface. The protein corona (PC), the set of proteins binding to the NPs surface, plays a critical role in particle recognition by the innate immune system. Still, in vitro incubation offers a limited understanding of biological interactions and fails to explain the in vivo fate. To date, several reports explained the impact of PC in vitro but its applications in the clinical field have been very limited. Furthermore, PC is often considered as a biological barrier reducing the targeting efficiency of nano vehicles. But the protein binding can actually be controlled by altering PC both in vitro and in vivo. Analyzing PC in vivo could accordingly provide a deep understanding of its biological effect and speed up the transfer to clinical applications. This review demonstrates the need for clarifications on the effect of PC in vivo and the control of its behavior by changing its physicochemical properties. It unfolds the recent in vivo developments to understand mechanisms and challenges at the nano-bio interface. Finally, it reports recent advances in the in vivo PC to overcome and control the limitations of the in vitro PC by employing PC as a boosting resource to prolong the NPs half-life, to improve their formulations and thereby to increase its use for biomedical applications.

International audience; Introduction. The objective of this study was to evaluate the feasibility and toxicity of superparamagnetic iron oxide nanoparticles (SPIONs) administered into the cochlea through the round window (RW) by an external magnetic field. Materials and Methods. In 5 Wistar rats, the left RW was punctured. SPIONs suspended in hyaluronic gel (5 mg/mL) were applied in the RW niche and covered by a muscle graft. The nanoparticles were mobilized using a rare earth magnet (0.54 T) held in 4 consecutive positions around the head. The right ear served as control. Hearing function was monitored by auditory brainstem responses (4-32 kHz tone bursts). Results. The auditory thresholds remained unchanged 1 month after the administration. The histological study of the cochleae showed that SPIONs were driven into the scala tympani in the basal turn, the second turn, and the apex. Conclusion. Superparamagnetic nanoparticles can be driven inside the cochlea toward the apex with a preserved hearing up to 1 month in rats.

In this study, Superparamagnetic iron oxide nanoparticles (SPION) were functionalized in one pot with two organic molecules. Firstly, polyethylene glycol (PEG) was mixed for 46 hours to improve steric stability and then, two hours before the end of the reaction, dimercaptosuccinic acid (DMSA) was added to provide negative charges and thiol groups for post-functionalization. Three different molecular weights of PEG were used (550, 2000 and 5000 g mol-1). The main goal of this study was to characterize and quantify accurately the surface of SPION functionalized with two organic molecules. We demonstrated the advantages of coupling thermogravimetric and X-ray photoelectron spectrometry analyses to distinguish accurately the covering of SPION's surface. Thanks to the combination of these two techniques we were able to distinguish the amount of DMSA and PEG on SPION regarding the length of the polymer. We also showed that the length of the PEG influenced the quantity of DMSA adsorbed. With the smallest PEG (550 g mol-1) the presence of DMSA is almost ten times higher than with the two other PEG used proving that long polymers prevent the adsorption of small molecules on the surface of SPION.

In this work, new nanohybrids based on superparamagnetic iron oxide nanoparticles (SPIONs) were elaborated and discussed for the first time as nanovectors of a derivative molecule of trans-resveratrol (RSV), a natural antioxidant molecule, which can be useful for brain disease treatment. The derivative molecule was chemically synthesized (4&rsquo, hydroxy-4-(3-aminopropoxy) trans-stilbene: HAPtS) and then grafted onto SPIONs surface using an organosilane coupling agent, which is 3-chloropropyltriethoxysilane (CPTES) and based on nucleophilic substitution reactions. The amount of HAPtS loaded onto SPIONs surface was estimated by thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS) analyses at 116 &micro, mol&middot, g&minus, 1 SPIONs. The synthesized HAPtS molecule, as well as the associated nanohybrids, were fully characterized by transmission electron microscopy (TEM), XPS, TGA, infrared (IR) and UV-visible spectroscopies, dynamic light scattering (DLS), and zeta potential measurements. The in vitro biological assessment of the synthesized nanohybrid&rsquo, s efficiency was carried out on C6 glioma cells and showed that the nanovector SPIONs-CPTES-HAPtS do not affect the mitochondrial metabolism (MTT test), but damage the plasma membrane (FDA test), which could contribute to limiting the proliferation of cancerous cells (clonogenic test) at a HAPtS concentration of 50 &micro, M. These nanoparticles have a potential cytotoxic effect that could be used to eliminate cancer cells.

International audience; The lack of toxicological data on nanomaterials makes it difficult to assess the risk related to their exposure, and as a result further investigation is required. This chapter presents the synthesis of controlled oxide nanoparticles followed by the evaluation of their safety profile or toxicity (iron, titanium and zinc oxides). The controlled surface chemistry, dispersion in several media, morphology and surface charge of these nanoparticles are presented (transmission electron microscopy, dynamic light scattering, zeta potential, X-ray photoelectron spectroscopy). Classical cytotoxic and cellular uptake studies on different cancer cell lines from liver, prostate, heart, brain and spinal cord are discussed. The incidence of nanoparticles on biogenesis and activity of cell organelles is also highlighted, as well as their biodistribution in animal models. The acute toxicity on zebrafish embryo model is also presented. Finally, the stress is put on the influence and the necessity of controlling the protein corona, a layer of plasma proteins physically adsorbed at the surface of such nanoparticles as a result of their presence in the bloodstream (or relevant biological fluids).

For the first time, phosphonate-functionalized magnetite nanoparticles (Fe3O4 NPs) were synthesized using a one-step continuous hydrothermal process. The NP surface was modified using a hydrophilic organic molecule, namely 6-phosphonohexanoic acid (PHA). NPs were fully characterized (TEM, XRD, DLS, ζ-potential, TGA, FTIR, XPS and specific surface area measurements) in order to investigate PHA effect on size, oxidation state, anchoring and colloidal stability. PHA reduced the crystallite size and size distribution and improved greatly colloidal stability when compared with bare Fe3O4 NPs. Moreover, PHA was grafted on the NP surface according to three different conformations: as mononuclear monodendates, as binuclear bidentates or as lying-down complexes. This report is very promising regarding the stabilization and functionalization of Fe3O4 NPs by phosphonate molecules under continuous hydrothermal conditions. The post-grafting of polymers such as polyethylene glycol can be considered owing to the presence of free carboxyl groups (-COOH) on the surface of Fe3O4 NPs.

Nanocomposite films composed of gold nanoparticles (AuNPs) embedded in a TiO 2 matrix have been prepared by direct liquid injection chemical vapor deposition process, using preformed nanoparticles and titanium isopropoxide as precursors. The spherical AuNPs about 4.1 nm in diameter were synthesized by using gold (III) chloride trihydrate and stabilized by thiol ligands. The depositions were carried out by performing at first oxide deposition, then gold nanoparticle one and capping with oxide. The morphology, structure; the chemical state and optical properties of nanocomposite films were characterized by scanning electron microscopy, Raman, X-ray photoelectron and UV–Vis absorption spectroscopies, respectively. The stability of the films upon thermal annealing up to 800 °C was studied.

International audience; Iron oxide nanoparticles have the capability to cross Blood Brain Barrier (BBB) and hence are widely investigated for biomedical operations in the central nervous system. Before being used in humans, it is necessary to investigate their biocompatibility, dosimetry and biological interaction. In the present study, in-house synthesized superparamagnetic iron oxide nanoparticles (SPIONs) were functionalized using the polymer, PolyEthylene Glycol and a fluorophore (Rhodamine) (fSPIONs). The interaction of fSPIONs with murine oligodendrocytes 158N revealed that the nanoparticles were taken up by the cells via endocytosis, and there was a dose-dependent increase in the intracellular iron content as revealed by flow cytometry, transmission electron microscopy and confocal microscopy. Nanoparticles remained stable inside the cells even after 24 h. In addition, interaction and/or accumulation of nanoparticles was supported by the possibility to isolate treated cells even after 24 h. Cell sorting capacity using a magnet depended on the amount of particles. Noteworthy, whereas these nanoparticles can interact per cell. fSPIONs exhibited good biocompatibility as no toxicological response, including morphological changes, loss of viability, oxidative stress or inflammatory response (IL-1β, IL-6 secretion) was observed. These data show that the in-house synthesized fSPIONs have no accumulate on 158N oligodendrocytes without the side effects on 158N cells, and constitute interesting tools for biomedical applications on nerve cells, including cellular imaging and targeting (oxidative stress, inflammation and cell death) that could be detrimental when a subsequent use of these nanoparticles in humans is considered.

Titanate nanotubes (TiONts) are promising agents for biomedical applications. Microglial activation and associated oxidative burst are major challenges in drug delivery applications across the brain. Here, TiONts were designed for drug delivery systems by functionalizing them with (3-aminopropyl) triethoxysilane (APTES), their interactions and biocompatibility were studied in vitro using murine microglial BV-2 cells. TiONts-APTES exposure resulted in increased ROS production and transient mitochondrial hyperpolarization. However, there was no indication of microglial proliferation in BV-2 cells as suggested by cell cycle analysis and morphology evaluation. The endocytosis as well as passive diffusion mediated TiONts-APTES internalization were proved by transmission electron microscopy (TEM) with and without amiloride, an endocytosis inhibiting agent. In addition, the TiONts-APTES exhibited good biocompatibility on microglial BV-2 cells as revealed by the plasma membrane integrity, lysosmal membrane integrity, morphology and viability analysis.

International audience; TiONts-phthalocyanine nanohybrids combining an efficient optical probe and a promising nanovector have been developed in a step-by-step approach and were thoroughly characterized. Each 150 nm long TiONts-Pc bear ca. 450 Pc. Three nanohybrids were prepared including three different linkers in quest for the best stability.

The use of a liquid injection delivery system to form composite films containing nanoparticles was investigated. Al 2 O 3 –TiO 2 films were grown on silicon substrates by direct liquid injection MOCVD (DLI-MOCVD) at 400 °C. The α-Al 2 O 3 nanoparticles (α-Al 2 O 3 NPs) dispersed in TiO 2 films resulted from co-deposition using colloidal α-Al 2 O 3 solution and titanium tetraisopropoxide as titanium precursor. Scanning electron microscopy coupled with EDS as well as Raman spectroscopy confirmed the presence of α-Al 2 O 3 NPs aggregates embedded in the TiO 2 matrix. The liquid injection system coupled with CVD technique can be promising to form composite films containing preformed nanoparticles.

IF 4.029; International audience; In this work, we discuss for the first time the elaboration of nanohybrid materials, intended for drug delivery systems, based on titanate nanotubes (TiONts) coated with chitosan polymer (CT). Chitosan has been used to enhance the biocompatibility of hydrothermally synthesized nanotubes in biological medium as a substitute for the polyethylene glycol (PEG) that is generally used for biocompatibility. CT grafting was carried out using two different approaches; the first was made by a covalent bond using two intermediate molecules, and the second is based on electrostatic interactions between CT and TiONts. The type of elaborated bond on the surface of TiONts was proven to influence the colloidal stability of the elaborated nanohybrids, which were studied in different media. A detailed comparison between these two approaches was carried by XPS and TGA-SM techniques. Finally, an original and sensitive cytotoxicity assay consisting of the measurement of the cells' total RNA synthesis was used to prove the non-toxicity of both obtained nanohybrids.

International audience; The search for convenient molecular probes for detecting DNA and RNA quadruplexes in vitro is marked by a rapid pace of progress, spurred on by the multiple roles these higher-order nucleic acid structures play in many genetic dysregulations. Here, we contribute to this search, reporting on a palladated porphyrin named Pd.TEGPy: its efficiency as quadruplex-selective fluorescent dye relies on a structural design that endows it with attractive supramolecular and electronic properties and makes it an efficient turn-on, quadruplex-selective fluorescent stain thanks to a DNA-mediated sensitization mechanism that ensures a high level of specificity.

« La separation des pouvoirs est devenue un slogan utilise dans tous les compartiments de la vie politique et du droit constitutionnel. C’est notamment le cas pour deux dispositions : l’interdiction faite au President de la Republique de penetrer dans les assemblees parlementaires et le principe selon lequel les commissions d’enquete parlementaires ne sauraient mener des investigations touchant a la president de la Republique. Dans les deux cas, il est demontre que la separation des pouvoirs n’est pas en cause mais la dignite de la fonction presidentielle ou l’histoire politique francaise. »

Ligand exchange on [Au25(SCH2CH2Ph)18−] [TOA+] is studied with two chiral ligands R/S-BINAS and NILC/NIDC in THF with induction of metal-based optical activity. Under the applied condition the ligand exchange is only partial, showing that also within a mixed ligand shell significant optical activity can be induced. The ligand exchange resulted in the change of particle size as observed by UV−vis spectroscopy.

The cationic organometallic aqua complexes formed by hydrolysis of [(C6H6)2RuCl2]2 in water, mainly [(C6H6)Ru(H2O)3]2+, intercalate into white sodium hectorite, replacing the sodium cations between the anionic silicate layers. The yellow hectorite thus obtained reacts in water with molecular hydrogen (50 bar, 100 °C) to give a dark suspension containing a black hectorite in which large hexagonally shaped ruthenium nanoparticles (20–50 nm) are intercalated between the anionic silicate layers, the charges of which being balanced by hydronium cations. If the reduction with molecular hydrogen (50 bar, 100 °C) is carried out in various alcohols, spherical ruthenium nanoparticles of smaller size (3–38 nm depending on the alcohol) are obtained. In alcohols other than methanol, the reduction also works without H2 under reflux conditions, the alcohol itself being the reducing agent; the ruthenium nanoparticles obtained in this case are spherical and small (2–9 nm) but tend to aggregate to form clusters of nanoparticles. Whereas the ruthenium nanoparticles prepared by reduction of the yellow hectorite in refluxing alcohols without hydrogen pressure are almost inactive, the nanoparticles formed by hydrogen reduction catalyze the hydrogenation of benzene to give cyclohexane under mild conditions (50 °C) with turnover frequencies up to 6500 catalytic cycles per hour, the best solvent being ethanol.

Liquid-crystalline dendrons carrying either a thiol or disulfide function which display nematic, smectic A, columnar, or chiral nematic phases have been synthesized. Their mesomorphic properties are in agreement with the nature of the mesogenic units and structure of the dendrons. The first-generation poly(aryl ester) dendron containing two cyanobiphenyl mesogenic units was used to functionalize gold nanoparticles. For full coverage, a smectic-like supramolecular organization on the nanometer scale is observed, when the gold nanoparticles are spread onto carbon-coated copper grids. This result indicates that the dendritic ligands reported here act as self-organization promoters.

Atherosclerosis is an inflammatory disease associated with the formation of atheroma plaques likely to rupture in which platelets are involved both in atherogenesis and atherothrombosis. The rupture is linked to the molecular composition of vulnerable plaques, causing acute cardiovascular events. In this study we propose an original targeted contrast agent for molecular imaging of atherosclerosis. Versatile USPIO (VUSPIO) nanoparticles, enhancing contrast in MR imaging, were functionalised with a recombinant human IgG4 antibody, rIgG4 TEG4, targeting human activated platelets. The maintenance of immunoreactivity of the targeted VUSPIO against platelets was confirmed in vitro by flow cytometry, transmission electronic and optical microscopy. In the atherosclerotic ApoE −/− mouse model, high-resolution ex vivo MRI demonstrated the selective binding of TEG4-VUSPIO on atheroma plaques. It is noteworthy that the rationale for targeting platelets within atherosclerotic lesions is highlighted by our targeted contrast agent using a human anti-αIIbβ3 antibody as a targeting moiety. From the Clinical Editor Current clinical assessment of atherosclerotic plagues is suboptimal. The authors in the article designed functionalized superparamagnetic iron oxide nanoparticles with TEG4, a recombinant human antibody, to target activated platelets. By using MRI, these nanoparticles can be utilized to study the process of atheroma pathogenesis.

International audience; The combination of anticancer drugs and metal oxide nanoparticles is of great interest in cancer nanomedicine. Here, the development of a new nanohybrid, titanate nanotube-docetaxel (TiONts-DTX) is reported, the two parts of which are conjugated by covalent linkages. Unlike most nanoparticles currently being developed for biomedical purposes, TiONts present a needle-shaped morphology. The surface of TiONts is linked with 3-aminopropyl triethoxysilane and with a hetero-bifunctional polymer (polyethylene glycol) to create well-dispersed and biocompatible nanovectors. The prefunctionalized surface of this scaffold has valuable attachments to graft therapeutic agents (DTX in our case) as well as chelating agents (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) to monitor the nanohybrids. To evaluate drug efficacy, in vitro tests have demonstrated that the association between TiONts and DTX shows cytotoxic activity against a hormone-refractory prostate cancer cell line (22Rv1) whereas TiONts without DTX do not. Finally, the first in vivo tests with intratumoral injections show that more than 70% of TiONts nanovectors are retained within the tumor for at least 7 d. Moreover, tumor growth in mice receiving TiONts-DTX is significantly slower than that in mice receiving free DTX. This nanohybrid can thus become a promising new tool in biomedicine to fight against prostate cancer.

In the present study, we report the dispersion of titanate nanotubes (TiONts) via polymer grafting (PolyEthylene Glycol, PEG) or polymer adsorption (polyethylene imine, PEI) where different TiONts/polymer ratios have been investigated. The TiONts/PEI and TiONts/PEG nanohybrids were characterized by scanning and transmission electron microscopy as well as by zeta potential measurements in order to determine both their dispersion state and stability in water (at different pH for zetametry). The nature of the chemical bonds at the surface of these nanohybrids was investigated by Fourier-transformed infrared (FTIR) spectroscopy while the grafting densities of PEG on the nanotubes were quantified by thermogravimetric analyses (TGA). The nanohybrids reported here are promising tools for biotechnology applications due to their tubular morphology, their very good dispersion in water and the reactivity of their surface.

The synthesis of the title compound, [FePtCl2(C15H14O2P)2]·0.5CH2Cl2, has been achieved by reacting PtCl2(PhCN)2 with the 1,1′-bis­[bis­(5-methyl-2-furyl)phosphino]ferrocene chelating ligand. The environment at the Pt atom can be described as distorted square-planar, with two cis-Cl atoms and two cis-P atoms.

International audience

Size exclusion chromatography (SEC) on a semipreparative scale (10 mg and more) was used to size-select ultrasmall gold nanoclusters (2 nm) from polydisperse mixtures. In particular, the ubiquitous byproducts of the etching process toward Au(38)(SR)(24) (SR, thiolate) clusters were separated and gained in high monodispersity (based on mass spectrometry). The isolated fractions were characterized by UV-vis spectroscopy, MALDI mass spectrometry, HPLC, and electron microscopy. Most notably, the separation of Au(38)(SR)(24) and Au(40)(SR)(24) clusters is demonstrated.

Herein we report the studies of Heck alkynylation (copper-free Sonogashira) with aryl halides (I, Br, Cl) employing various metallic precursors, tertiary phosphanes and bases in [BMIM][BF4] as the solvent. As a result, we provide the first method that allows the coupling of a large array of substrates, either activated or deactivated bromides in an ionic liquid. Furthermore, the system of highest efficiency is unexpectedly the simplest and cheaper combination that employs [Pd(η3-C3H5)Cl]2/PPh3 at only a 1 mol-% loading with pyrrolidine as the base and in the absence of a copper salt. The coupling of sterically and electronically deactivated bromides bearing different functional groups to aryl- and alkyl acetylenes, as well as the possibility of recycling, make these results of high interest to the future development of Heck- and Sonogashira-type reactions in ionic liquids.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

41 Background: From 30% to 50% of high risk prostate cancer patients who undergo radiation therapy (RT) will have a biochemical failure. Combining chemotherapy, such as Docetaxel (DXL), with RT can enhance its efficiency. Multidrug resistance mechanisms often limit drug efficacy by decreasing tumor cell intracellular concentration of drugs. There is interest to develop nanocarrier of DXL to maintain drug inside cancer cells by improving its efficacy. The purpose of this study was to develop a titanate-nanotube (TiONt)-DXL nanocarrier (nanohybrid) and to evaluate its in vivobiodistribution as well as its radiosensitizing efficacy in association with RT on a hormone-independent prostate cancer model. Methods: DXL molecules were grafted on TiONts using PEG-3000 molecules to generate the nanohybrid. In vitrocytotoxic activity of the nanohybrid was evaluated on PC-3 cell line using MTS assay. After intratumoral injection, biodistribution analysis was performed by SPEC-CT imaging of mice bearing subcutaneous PC-3 human prostate tumors. To evaluate the benefit of nanohybrid and RT association, tumors were irradiated using 3 fractions of 4Gy administrated after the injection of nanohybrids. Nine groups of 7 mice were used to evaluate nanohybrid and RT association efficacy : untreated, control with buffer IT injection, +/- RT, free DXL, +/- RT, TiONt +/- RT and TiONt-DXL +/- RT. Mice behavior, health status and tumor volume were monitored twice a week until tumor growth recovery. Results: Biodistribution kinetics showed that more than 70% of nanohybrids were localized into the tumor 96 hours after injection. Mice receiving nanohybrid-RT exhibited a significant tumor growth delay to reach a volume of 1,000mm3compared to mice receiving free DXL-RT: 73.7 days (median, [58.9-89]) vs 56 days (median, [31.5-74]) (p=0.0127). Conclusions: TiONt-DXL improves RT efficacy compared to free DXL. These results suggest that local control might be enhanced by TiONt-DXL. TiONt-DXL can be injected as a radiosensitizer in men harboring high risk localized prostate cancer with needles during prostate brachytherapy procedure.

Chiral metal surfaces and nanoparticles have the potential to be used for the selective production, the resolution and the detection of enantiomers of a chiral compound, which renders them highly attractive in view of the tremendous consequences of homochirality on earth. Their capability to distinguish between enantiomers of a chemical compound relies on their structure and the ability to form intermolecular interactions. However, molecular-level understanding of the interactions that are at the origin of enantiodiscrimination is lagging behind due to the lack of powerful experimental techniques that are able to spot these interactions selectively with high sensitivity. In this article two techniques based on infrared spectroscopy are presented that are able to selectively target the chiral properties of nanoparticles and interfaces. These are the combination of attenuated total reflection infrared (ATR-IR) with modulation excitation spectroscopy (MES) to probe enantiodiscriminating interactions at chiral solid–liquid interfaces and vibrational circular dichroism (VCD), which is used to probe the structure of chirally modified metal nanoparticles.

A SPIO-phthalocyanine nanohybrid is developed as a bimodal contrast agent for Optical and Magnetic Resonance Imaging. The organic coating was covalently attached onto SPIO in a step-by-step approach. Each coated-SPIO was thoroughly characterized. The hydrodynamic size of the SPIO-Pc is ca. 60 nm with a coverage of ca. 690 Pc/SPIO.

La doctrine juridique francaise, depuis la fin du xixe siecle, qualifie de « rigide » la separation des pouvoirs aux Etats-Unis. Cette vue est erronee : tributaire des enjeux politiques de la IIIe Republique, elle meconnait les traits saillants du regime americain. Celui-ci est caracterise par une interdependance des organes (sous reserve des membres du Congres) et par leur collaboration dans l’accomplissement des fonctions etatiques.

Mallet du Pan est un temoin precieux de la Revolution Francaise. Il jugera severement sa radicalisation. Avec ses amis monarchiens, Mallet est un apotre de la liberte : il pense qu’elle sera mieux assuree par la monarchie, a condition que celle-ci proscrive les « abus » de l’ancien regime, notamment la societe d’ordres. La preference pour la monarchie est incontestable – sans que la restauration dut emprunter la voie des armes – car la republique est impraticable dans un pays comme la France.