Design and characterization of magnetic nano-objects for Magnetic Resonance Imaging (MRI)

Les nanoparticules magnétiques d'oxyde de fer (NPs) fonctionnalisées sont des objets très étudiés pour le développement d'agents de contraste pour l'IRM. Cependant, il reste des challenges à lever comme: optimiser la fonctionnalisation des NPs sans altérer leurs propriétés magnétiques tout en assurant leur biocompatibilité et leur furtivité dans le corps humain ; empêcher la désorption des molécules greffées dans les conditions in-vivo ; avoir une taille moyenne des particules en suspension inférieure à 100 nm. Dans ce contexte nous proposons une approche originale qui consiste à greffer à la surface de NPs des molécules dendritiques (favorisant la stabilité des suspensions par interaction stérique et constituant une plateforme pour le greffage de molécules fonctionnelles) avec un agent de couplage phosphonate (permettant un ancrage direct et fort des molécules) pour concevoir des agents de contrastes performants et innovants. Ainsi, des NPs d'une taille moyenne de 10 nm ont été synthétisées par deux méthodes: la co-précipitation et la décomposition thermique. Trois dendrons ont été conçus sur la base d'un coeur aromatique possédant d'un côté l'agent de couplage phosphonate, de l'autre trois chaines biocompatibles oligoéthylène glycol portant des groupes fonctionnels tels COOH ou NH2. Les conditions de greffage ont été mises au point suivant le type de NPs et le type de dendrons. Les nombreuses caractérisations des NPs et de leurs suspensions montrent que les propriétés magnétiques et structurales des NPs sont préservées après l'étape de greffage. Les mesures de relaxivité, des tests in-vivo et des mesures IRM ont montré le grand potentiel de ces NPs dendronisées pour l'IRM.Functionalized iron oxide nanoparticles (NPs) have attracted an increasing interest as contrast agents for MRI. However, challenges remain to overcome: to optimize the functionalization of nanoparticles without affecting their magnetic properties while ensuring their biocompatibility and stealth in the human body, to prevent desorption of the grafted molecules under in vivo conditions, to ensure a small particle size distribution below 100 nm In this context, we propose a novel strategy which involves the grafting, at the surface of NPs, of dendritic molecules (favoring the suspensions stability by steric hindrance and constituting a platform for the grafting of functional molecules) via a phosphonate coupling agent (allowing a direct grafting and a stronger binding) to develop innovative and competitive contrast agents. Thus, NPs with an average size of 10 nm were synthesized by two methods: co-precipitation and thermal decomposition. Three hydrophilic oligoethyleneglycol-based dendrons displaying a phosphonic acid at the focal point and three biocompatible chains (oligoethylene glycol) bearing functional groups such as COOH or NH2 were designed. The grafting conditions have been adapted according to the NPs and dendron natures. Numerous characterizations of the nanoparticles and their suspensions showed the preservation of the NPs magnetic and structural properties after the grafting step. Relaxivity measurements, in vivo tests and MRI measurements have shown the great potential of these dendronized nanoparticles for MRI

Optimization of Magnetic Inks Made of L10-Ordered FePt Nanoparticles and Polystyrene-block-Poly(ethylene oxide) Copolymers.

The preparation of magnetic inks stable over time made of L10-ordered FePt nanoparticles, thiol-ended poly(ethylene glycol) methyl ether (mPEO-SH) compatibilizing macromolecules and asymmetric polystyrene-block-poly(ethylene oxide) copolymers (BCP) as a subsequent self-organizing medium was optimized. It was demonstrated that the use of sacrificial MgO shells as physical barriers during the annealing stage for getting the L10-ordered state makes easier and more efficient the anchoring of compatibilizing PEO macromolecules onto the nanoparticles surface. L10-FePt grafted nanoparticles have shown a good colloidal stability and affinity with the PEO domains of the BCP leading to L10-FePt/BCP composite thin layers with individual magnetic dots dispersed in the BCP matrix.

Effect of the nanoparticle synthesis method on dendronized iron oxides as MRI contrast agents

Équipe 401 : Nanomatériaux pour la vie et développement durableInternational audienceAqueous suspensions of dendronized iron oxide nanoparticles (NPs) have been obtained after functionalization, with two types of dendrons, of NPs synthesized either by coprecipitation (leading to naked NPs in water) or by thermal decomposition (NPs in situ coated by oleic acid in an organic solvent). Different grafting strategies have been optimized depending on the NPs synthetic method. The size distribution, the colloidal stability in isoosmolar media, the surface complex nature as well as the preliminary biokinetic studies performed with optical imaging, and the contrast enhancement properties evaluated through in vitro and in vivo MRI experiments, have been compared as a function of the nature of both dendrons and NPs. All functionalized NPs displayed good colloidal stability in water, however the ones bearing a peripheral carboxylic acid function gave the best results in isoosmolar media. Whereas the grafting rates were similar, the nature of the surface complex depended on the NPs synthetic method. The in vitro contrast enhancement properties were better than commercial products, with a better performance of the NPs synthesized by coprecipitation. On the other hand, the NPs synthesized by thermal decomposition were more efficient in vivo. Furthermore, they both displayed good biodistribution with renal and hepatobiliary elimination pathways and no consistent RES uptake

From core–shell BaTiO3@MgO to nanostructured low dielectric loss ceramics by spark plasma sintering

We report a quite general way to design materials with tailored properties by combining thermolysis and fast sintering approaches. Submicrometric-sized BaTiO3 particles have been directly coated in a continuous nanocrystalline MgO shell through a thermal decomposition process. The electron microscopy study has evidenced a shell composed of randomly oriented MgO nanocrystallites. The final nanostructured composite, made of sub-micrometric MgO and BaTiO3 grains uniformly distributed, is obtained in situ during the SPS process. Such a rearrangement can be explained by the initial core–shell architecture, the weak cohesion of the MgO nanocrystallites and their soft plastic behavior under SPS conditions. The composite effect leads to significant modifications in both the dielectric properties and Curie–Weiss parameters compared to uncoated BaTiO3, especially a decrease and thermal stabilization of both the permittivity and the dielectric losses. We ascribe such changes to the stress generated during SPS through the extended interfaces between the two components

Dendronized iron oxide nanoparticles for multimodal imaging

The synthesis of small-size dendrons and their grafting at the surface of iron oxide nanoparticles were achieved with the double objective to obtain a good colloidal stability with a mean hydrodynamic diameter smaller than 100 nm and to ensure the possibility of tuning the organic coating characteristics including morphology, functionalities, physico-chemical properties, grafting of fluorescent or targeting molecules. Magnetic resonance and fluorescence imaging are then demonstrated to be simultaneously possible using such versatile superparamagnetic iron oxide nanocrystals covered by a dendritic shell displaying either carboxylate or ammonium groups at their periphery which could be further labelled with a fluorescent dye. The grafting conditions of these functionalized dendrons at the surface of SPIO NPs synthesized by co-precipitation have been optimized as a function of the nature of the peripheral functional group. The colloidal stability has been investigated in water and osmolar media, and in vitro and in vivo MRI and optical imaging measurements have been performed showing encouraging biodistribution. (C) 2011 Elsevier Ltd. All rights reserved

Effect of the nanoparticle synthesis method on dendronized iron oxides as MRI contrast agents

Aqueous suspensions of dendronized iron oxide nanoparticles (NPs) have been obtained after functionalization, with two types of dendrons, of NPs synthesized either by coprecipitation (leading to naked NPs in water) or by thermal decomposition (NPs in situ coated by oleic acid in an organic solvent). Different grafting strategies have been optimized depending on the NPs synthetic method. The size distribution, the colloidal stability in isoosmolar media, the surface complex nature as well as the preliminary biokinetic studies performed with optical imaging, and the contrast enhancement properties evaluated through in vitro and in vivo MRI experiments, have been compared as a function of the nature of both dendrons and NPs. All functionalized NPs displayed good colloidal stability in water, however the ones bearing a peripheral carboxylic acid function gave the best results in isoosmolar media. Whereas the grafting rates were similar, the nature of the surface complex depended on the NPs synthetic method. The in vitro contrast enhancement properties were better than commercial products, with a better performance of the NPs synthesized by coprecipitation. On the other hand, the NPs synthesized by thermal decomposition were more efficient in vivo. Furthermore, they both displayed good biodistribution with renal and hepatobiliary elimination pathways and no consistent RES uptake