Pascal Perriat

The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy

A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5u2009nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed.

Sintering of copper nanopowders under hydrogen: an in situ X-ray diffraction analysis

Abstract The reduction by hydrogen gas of the cuprite layer on copper nanocrystals and the subsequent sintering of the nano-particles were studied using in-situ X-ray diffraction and dilatometry. Spherical nanocrystals produced by evaporation and condensation have an average size of 35 nm, exhibiting a large surface curvature. Each nanoparticle is coated with a 3.5 nm layer of Cu 2 O, which is rough and disordered, as revealed by high-resolution electron microscopy. Reduction by hydrogen of this curved cuprite layer occurs at 363 K, which is ≈65 K lower than is observed on a layer supported by micrometer-sized or bulk copper with a flat surface. The reduction process and its effect on the sintering of nanopowders are analysed and discussed.

Biodistribution of ultra small gadolinium-based nanoparticles as theranostic agent: Application to brain tumors

Gadolinium-based nanoparticles are novel objects with interesting physical properties, allowing their use for diagnostic and therapeutic applications. Gadolinium-based nanoparticles were imaged following intravenous injection in healthy rats and rats grafted with 9L gliosarcoma tumors using magnetic resonance imaging and scintigraphic imaging. Quantitative biodistribution using gamma-counting of each sampled organ confirmed that these nanoparticles were rapidly cleared essentially by renal excretion. Accumulation of these nanoparticles in 9L gliosarcoma tumors implanted in the rat brain was quantitated. This passive and long-duration accumulation of gadolinium-based nanoparticles in tumor, which is related to disruption of the blood–brain barrier, is in good agreement with the use of these nanoparticles as radiosensitizers for brain tumors.

Multifunctional ultrasmall nanoplatforms for vascular-targeted interstitial photodynamic therapy of brain tumors guided by real-time MRI

Photodynamic therapy (PDT) for brain tumors appears to be complementary to conventional treatments. A number of studies show the major role of the vascular effect in the tumor eradication by PDT. For interstitial PDT (iPDT) of brain tumors guided by real-time imaging, multifunctional nanoparticles consisting of a surface-localized tumor vasculature targeting neuropilin-1 (NRP-1) peptide and encapsulated photosensitizer and magnetic resonance imaging (MRI) contrast agents, have been designed. Nanoplatforms confer photosensitivity to cells and demonstrate a molecular affinity to NRP-1. Intravenous injection into rats bearing intracranial glioma exhibited a dynamic contrast-enhanced MRI for angiogenic endothelial cells lining the neovessels mainly located in the peripheral tumor. By using MRI completed by NRP-1 protein expression of the tumor and brain adjacent to tumor tissues, we checked the selectivity of the nanoparticles. This study represents the first in vivo proof of concept of closed-head iPDT guided by real-time MRI using targeted ultrasmall nanoplatforms. From the clinical editor: The authors constructed tumor vascular peptide targeting multifunctional silica-based nanoparticles, with encapsulated gadolinium oxide as MRI contrast agent and chlorin as a photosensitizer, as a proof of concept novel treatment for glioblastoma in an animal model.

Surface adsorption effects on the lattice expansion of copper nanocrystals

Lattice expansion in nanocrystalline copper due to size and surface effect is reported. The lattice parameter is measured by in situ x-ray diffraction at various temperatures from −173°Cto150°C. The experiments are carried out on nanocrystalline copper powders having an average particle size of 40nm. The size effect on the lattice expansion is examined regarding a modified Laplace law, where a surface stress is considered instead of the usual scalar surface energy. The results are discussed taking into account oxidation state and the sorption of molecular species at the nanoparticles surface.

Characterization of ferrites synthesized by mechanical alloying and soft chemistry

For the purpose of comparing nanostructured materials prepared by different synthesis methods, nanocrystalline Fe-based spinels were synthesized using two different routes: soft chemistry and high-energy ball milling. The as-prepared powders -were characterized notably by thermogravimetric analyses and 57Fe Mossbauer spectrometry.

Correlation Between the Reactivity Towards Oxygen and the Coercitivity in Submicron Vanadium Ferrite Spinels

Nanometric powders of Fe 2 VO 4 and Fe 1.84 V 0.92 Co 0.23 O 4 have been synthetised by chimie douce process The cations in the spinel structure can oxidize at low temperatures without any phase transformation leading to cation-deficient spinel with formula Fe 2 VO 4+δ and Fe 1.84 V 0.92 Co 0.23 O 4+δ , where δ is the deviation from stoichiometry, due to a change of the anion-cation ratio, consecutive to formation of vacancies. The oxidation, investigated by thermogravimetry, involves several stages, each stage corresponding to the oxidation of one oxidizable cation, Fe 2+ , V 2+ ,V 3+ on B (octahedral) or A (tetrahedral) sites. Coercivity has also been studied, revealing that the coercive field increases with the rate of oxidation.