Stéphane Mornet

Magnetic nanoparticle design for medical diagnosis and therapy

Magnetic nanoparticles have attracted attention because of their current and potential usefulness as contrast agents for magnetic resonance imaging (MRI) or colloidal mediators for cancer magnetic hyperthermia. This review examines these in vivo applications through an understanding of the involved problems and the current and future possibilities for resolving them. A special emphasis is made on magnetic nanoparticle requirements from a physical viewpoint (e.g. relaxivity for MRI and specific absorption rate for hyperthermia), the factors affecting their biodistribution (e.g. size, surface hydrophobic/hydrophilic balance, etc.) and the solutions envisaged for enhancing their half-life in the blood compartment and targeting tumour cells.

Magnetic nanoparticles and their applications in medicine

Magnetic nanoparticles have attracted attention in modern medicine and pharmacology owing to their potential usefulness as contrast agents for MRI, as colloidal mediators for cancer magnetic hyperthermia or as active constituents of drug-delivery platforms. This review examines these in vivo applications through an understanding of the involved problems and the current and future possibilities for resolving them. A special emphasis is placed upon magnetic nanoparticle requirements from a physical viewpoint (e.g., relaxivity for MRI, specific absorption rate for hyperthermia and magnetic guidance), the factors affecting their biodistribution after intravenous injection (e.g., size and surface hydrophobic/hydrophilic balance) and the solutions envisaged for enhancing their half-life in the blood compartment and in targeting tumor cells.

Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration

Plasma and other body fluids contain membranous extracellular vesicles (EVs), which are considered to derive from activated or apoptotic cells. EVs participate in physiological and pathological processes and have potential applications in diagnostics or therapeutics. Knowledge on EVs is, however, limited, mainly due to their sub‐micrometer size and to intrinsic limitations in methods applied for their characterization.

Nanoparticles of iron(II) spin-crossover

We report the synthesis of spin crossover 69 nm spherical nanoparticles of [Fe(NH2-trz)3](Br)2.3H2O.0.03(surfactant) (NH2trz = 4-amino-1,2,4-triazole, surfactant = Lauropal), prepared by the reverse micelle technique, which exhibit at room temperature a thermal hysteresis characterized by magnetic, diffuse reflectivity and Raman studies.

Fine Tuning of the Relaxometry of γ-Fe2O3@SiO2 Nanoparticles by Tweaking the Silica Coating Thickness

We report the fine-tuning of the relaxometry of gamma-Fe2O3@SiO2 core-shell nanoparticles by adjusting the thickness of the coated silica layer. It is clear that the coating thickness of Fe2O3@SiO2 nanoparticles has a significant impact on the r(1) (at low B0 fields), r(2), and r(2)* relaxivities of their aqueous suspensions. These studies clearly indicate that the silica layer is heterogeneous and has regions that are porous to water and others-that are not. It is also shown, that the viability and the mitochondrial dehydrogenase expression of the microglial cells do not appear to be sensitive to the vesicular load with these core-shell nanoparticles. The adequate silica-shell thickness can therefore be tuned to allow for both a sufficiently high response as contrast agent, and-adequate grafting of targeted biomolecules.

Deciphering the mechanisms of cellular uptake of engineered nanoparticles by accurate evaluation of internalization using imaging flow cytometry.

BackgroundThe uptake of nanoparticles (NPs) by cells remains to be better characterized in order to understand the mechanisms of potential NP toxicity as well as for a reliable risk assessment. Real NP uptake is still difficult to evaluate because of the adsorption of NPs on the cellular surface.ResultsHere we used two approaches to distinguish adsorbed fluorescently labeled NPs from the internalized ones. The extracellular fluorescence was either quenched by Trypan Blue or the uptake was analyzed using imaging flow cytometry. We used this novel technique to define the inside of the cell to accurately study the uptake of fluorescently labeled (SiO2) and even non fluorescent but light diffracting NPs (TiO2). Time course, dose-dependence as well as the influence of surface charges on the uptake were shown in the pulmonary epithelial cell line NCI-H292. By setting up an integrative approach combining these flow cytometric analyses with confocal microscopy we deciphered the endocytic pathway involved in SiO2 NP uptake. Functional studies using energy depletion, pharmacological inhibitors, siRNA-clathrin heavy chain induced gene silencing and colocalization of NPs with proteins specific for different endocytic vesicles allowed us to determine macropinocytosis as the internalization pathway for SiO2 NPs in NCI-H292 cells.ConclusionThe integrative approach we propose here using the innovative imaging flow cytometry combined with confocal microscopy could be used to identify the physico-chemical characteristics of NPs involved in their uptake in view to redesign safe NPs.

Cryo-electron tomography of nanoparticle transmigration into liposome

Nanoparticle transport across cell membrane plays a crucial role in the development of drug delivery systems as well as in the toxicity response induced by nanoparticles. As hydrophilic nanoparticles interact with lipid membranes and are able to induce membrane perturbations, hypothetic mechanisms based on membrane curvature or hole formation have been proposed for activating their transmigration. We report on the transport of hydrophilic silica nanoparticles into large unilamellar neutral DOPC liposomes via an internalization process. The strong adhesive interactions of lipid membrane onto the silica nanoparticle triggered liposome deformation until the formation of a curved neck. Then the rupture of this membrane neck led to the complete engulfment of the nanoparticle. Using cryo-electron tomography we determined 3D architectures of intermediate steps of this process unveiling internalized silica nanoparticles surrounded by a supported lipid bilayer. This engulfing process was achieved for a large range of particle size (from 30 to 200 nm in diameter). These original data provide interesting highlights for nanoparticle transmigration and could be applied to biotechnology development.

Surface modification of zinc oxide nanoparticles by aminopropyltriethoxysilane

Commercial zinc oxide nanoparticles (20–30 nm) were coated by aminopropyltriethoxysilane (APTES) under varying environments. Three different processes, acidic, basic and toluene were used. The effects of coating conditions (acidic, basic and toluene) on the grafting, structural and optical properties of these nanoparticles were studied. In the three cases, it was possible to control the coating and according to X-ray diffraction, BET, TEM and SEM results, it is clear that the APTES coating plays a role of growth inhibitor even at 800 °C...

Synthesis of non-spherical gold nanoparticles

Non-spherical gold nanoparticles such as rods (short, long) (1,2), wires, cubes (3), nanocages (4), (multi-)concentric shells (5), triangular prisms (6–7), as well as other more exotic structures such as hollow tubes, capsules (6), even branched nanocrystals (8–9) have garnered significant research attention in the past few years. They exhibit unique and fine-tuned properties which either strongly differ or are more pronounced from those of symmetric, spherical gold nanoparticles. Their unusual optical and electronic properties, improved mechanical properties and specific surface-enhanced spectroscopies make them ideal structures for emerging applications in photonics, electronics, optical sensing and imaging, biomedical labelling and sensing, catalysis and electronic devices among others (10,11,12,13,14,15,16,17,18). Furthermore, some of these anisotropic nanoparticles enable elucidation of the particle growth mechanism, which in turn makes it possible to predict and systematically manipulate the final nanocrystal morphology (8,19-20). Finally, these anisotropic gold nanomaterials provide templates for further generation of novel materials (21,22).This article provides an overview of current research in the area of anisotropic gold nanoparticles. We begin by outlining key properties that they possess; we then describe how to control their morphology. Some of the most innovative synthetic strategies are highlighted together with an emphasis on recent results from our laboratories as well as future perspectives for anisotropic gold nanoparticles as novel materials.

Gold nanorods coated with mesoporous silica shell as drug delivery system for remote near infrared light-activated release and potential phototherapy

In this study, we report the synthesis of a nanoscaled drug delivery system, which is composed of a gold nanorod-like core and a mesoporous silica shell (GNR@MSNP) and partially uploaded with phase-changing molecules (1-tetradecanol, TD, T(m) 39 °C) as gatekeepers, as well as its ability to regulate the release of doxorubicin (DOX). Indeed, a nearly zero premature release is evidenced at physiological temperature (37 °C), whereas the DOX release is efficiently achieved at higher temperature not only upon external heating, but also via internal heating generated by the GNR core under near infrared irradiation. When tagged with folate moieties, GNR@MSNPs target specifically to KB cells, which are known to overexpress the folate receptors. Such a precise control over drug release, combining with the photothermal effect of GNR cores, provides promising opportunity for localized synergistic photothermal ablation and chemotherapy. Moreover, the performance in killing the targeted cancer cells is more efficient compared with the single phototherapeutic modality of GNR@MSNPs. This versatile combination of local heating, phototherapeutics, chemotherapeutics and gating components opens up the possibilities for designing multifunctional drug delivery systems.