Jérôme Fresnais

A Universal Scaling Law to Predict the Efficiency of Magnetic Nanoparticles as MRI T2-Contrast Agents

Magnetic particles are very efficient magnetic resonance imaging (MRI) contrast agents. In recent years, chemists have unleashed their imagination to design multi-functional nanoprobes for biomedical applications including MRI contrast enhancement. This study is focused on the direct relationship between the size and magnetization of the particles and their nuclear magnetic resonance relaxation properties, which condition their efficiency. Experimental relaxation results with maghemite particles exhibiting a wide range of sizes and magnetizations are compared to previously published data and to well-established relaxation theories with a good agreement. This allows deriving the experimental master curve of the transverse relaxivity versus particle size and to predict the MRI contrast efficiency of any type of magnetic nanoparticles. This prediction only requires the knowledge of the size of the particles impermeable to water protons and the saturation magnetization of the corresponding volume. To predict the T(2) relaxation efficiency of magnetic single crystals, the crystal size and magnetization - obtained through a single Langevin fit of a magnetization curve - is the only information needed. For contrast agents made of several magnetic cores assembled into various geometries (dilute fractal aggregates, dense spherical clusters, core-shell micelles, hollow vesicles…), one needs to know a third parameter, namely the intra-aggregate volume fraction occupied by the magnetic materials relatively to the whole (hydrodynamic) sphere. Finally a calculation of the maximum achievable relaxation effect - and the size needed to reach this maximum - is performed for different cases: maghemite single crystals and dense clusters, core-shell particles (oxide layer around a metallic core) and zinc-manganese ferrite crystals.

Redispersible Hybrid Nanopowders: Cerium Oxide Nanoparticle Complexes with Phosphonated-PEG Oligomers

Rare earth cerium oxide (ceria) nanoparticles are stabilized using end-functional phosphonated-PEG oligomers. The complexation process and structure of the resulting hybrid core-shell singlet nanocolloids are described, characterized, and modeled using light and neutron scattering data. The adsorption mechanism is nonstoichiometric, yielding the number of adsorbed chains per particle N(ads) = 270 at saturation. Adsorption isotherms show a high affinity of the phosphonate head for the ceria surface (adsorption energy DeltaG(ads) approximately -16kT) suggesting an electrostatic driving force for the complexation. The ease, efficiency, and integrity of the complexation is highlighted by the formation of nanometric sized cerium oxide particles covered with a well anchored PEG layer, maintaining the characteristics of the original sol. This solvating brushlike layer is sufficient to solubilize the particles and greatly expand the stability range of the original sol (<pH 3) up to pH = 9. We underscore two key attributes of the tailored sol: (i) strong UV absorption capability after functionalization and (ii) ability to redisperse after freeze-drying as powder in aqueous or organic solvents in varying concentrations as singlet nanocolloids. This robust platform enables translation of intrinsic properties of mineral oxide nanoparticles to critical end use.

Functional Iron Oxide Magnetic Nanoparticles with Hyperthermia‐Induced Drug Release Ability by Using a Combination of Orthogonal Click Reactions

Click and drug: A combination of orthogonal click reactions is employed for the preparation of functional iron oxide nanoparticles (IONPs) that show unprecedented hyperthermia-induced drug release through a magnetically stimulated retro-Diels-Alder (rDA) process. Magnetic stimulation induces sufficient local energy in close proximity to the cycloadduct to initiate the rDA process

Electrosteric enhanced stability of functional sub-10 nm cerium and iron oxide particles in cell culture medium

Applications of nanoparticles in biology require that the nanoparticles remain stable in solutions containing high concentrations of proteins and salts, as well as in cell culture media. In this work, we developed simple protocols for the coating of sub-10 nm nanoparticles and evaluated the colloidal stability of dispersions in various environments. Ligands (citric acid), oligomers [phosphonate-terminated poly(ethylene oxide)], and polymers [poly(acrylic acid)] were used as nanometer-thick adlayers for cerium (CeO2) and iron (gamma-Fe2O3) oxide nanoparticles. The organic functionalities were adsorbed on the particle surfaces via physical (electrostatic) forces. Stability assays at high ionic strengths and in cell culture media were performed by static and dynamic light scattering. Of the three coatings examined, we found that only poly(acrylic acid) fully preserved the dispersion stability over the long term (longer than weeks). The improved stability was explained by the multipoint attachments of the chains onto the particle surface and by the adlayer-mediated electrosteric interactions. These results suggest that anionically charged polymers represent an effective alternative to conventional coating agents.

Poly(acrylic acid)-coated iron oxide nanoparticles: Quantitative evaluation of the coating properties and applications for the removal of a pollutant dye

In this work, 6-12 nm iron oxide nanoparticles were synthesized and coated with poly(acrylic acid) chains of molecular weight 2100 g mol(-1). Based on a quantitative evaluation of the dispersions, the bare and coated particles were thoroughly characterized. The number densities of polymers adsorbed at the particle surface and of available chargeable groups were found to be 1.9±0.3 nm(-2) and 26±4 nm(-2), respectively. Occurring via a multi-site binding mechanism, the electrostatic coupling leads to a solid and resilient anchoring of the chains. To assess the efficacy of the particles for pollutant remediation, the adsorption isotherm of methylene blue molecules, a model of pollutant, was determined. The excellent agreement between the predicted and the measured amounts of adsorbed dyes suggests that most carboxylates participate to the complexation and adsorption mechanisms. An adsorption of 830 mg g(-1) was obtained. This quantity compares well with the highest values available for this dye.

Growth mechanism of nanostructured superparamagnetic rods obtained by electrostatic co-assembly

We report on the growth of nanostructured rods fabricated by electrostatic co-assembly between iron oxide nanoparticles and polymers. The nanoparticles put under scrutiny, γ-Fe2O3 or maghemite, have diameter of 6.7 nm and 8.3 nm and narrow polydispersity. The co-assembly is driven by (i) the electrostatic interactions between the polymers and the particles, and by (ii) the presence of an externally applied magnetic field. The rods are characterized by large anisotropy factors, with diameter ∼200 nm and length comprised between 1 and 100 μm. In the present work, we provide for the first time the morphology diagram for the rods as a function of ionic strength and concentration. We show the existence of a critical nanoparticle concentration (cc = 10−3 wt.%) and of a critical ionic strength (IcS = 0.42 M) beyond which the rods do not form. In the intermediate regimes (c = 10−3–0.1 wt. % or IS = 0.35–0.42 M), only tortuous and branched aggregates are detected. At higher concentrations and lower ionic strengths, linear and stiff rods with superparamagnetic properties are produced. Based on these data, a mechanism for the rod formation is proposed. The mechanism proceeds in two steps: (i) the formation and growth of spherical clusters of particles, and (ii) the alignment of the clusters induced by the magnetic dipolar interactions. As far as the kinetics of these processes is concerned, the clusters growth and their alignment occur concomitantly, leading to a continuous accretion of particles or small clusters, and a welding of the rodlike structure.

Superparamagnetic iron oxide polyacrylic acid coated γ-Fe2O3 nanoparticles do not affect kidney function but cause acute effect on the cardiovascular function in healthy mice.

This study describes the distribution of intravenously injected polyacrylic acid (PAA) coated γ-Fe(2)O(3) NPs (10 mg kg(-1)) at the organ, cellular and subcellular levels in healthy BALB/cJ mice and in parallel addresses the effects of NP injection on kidney function, blood pressure and vascular contractility. Magnetic resonance imaging (MRI) and transmission electron microscopy (TEM) showed accumulation of NPs in the liver within 1h after intravenous infusion, accommodated by intracellular uptake in endothelial and Kupffer cells with subsequent intracellular uptake in renal cells, particularly the cytoplasm of the proximal tubule, in podocytes and mesangial cells. The renofunctional effects of NPs were evaluated by arterial acid-base status and measurements of glomerular filtration rate (GFR) after instrumentation with chronically indwelling catheters. Arterial pH was 7.46±0.02 and 7.41±0.02 in mice 0.5 h after injections of saline or NP, and did not change over the next 12 h. In addition, the injections of NP did not affect arterial PCO(2) or [HCO(3)(-)] either. Twenty-four and 96 h after NP injections, the GFR averaged 0.35±0.04 and 0.35±0.01 ml min(-1) g(-1), respectively, values which were statistically comparable with controls (0.29±0.02 and 0.33±0.1 ml(-1) min(-1) 25 g(-1)). Mean arterial blood pressure (MAP) decreased 12-24 h after NP injections (111.1±11.5 vs 123.0±6.1 min(-1)) associated with a decreased contractility of small mesenteric arteries revealed by myography to characterize endothelial function. In conclusion, our study demonstrates that accumulation of superparamagnetic iron oxide nanoparticles does not affect kidney function in healthy mice but temporarily decreases blood pressure.

Influence of the Formulation Process in Electrostatic Assembly of Nanoparticles and Macromolecules in Aqueous Solution: The Mixing Pathway

Complex Assemblies of Soft Matter Laboratory (COMPASS), CNRS UMI3254, Rhodia Center for Research and Technology in Bristol, 350 Georges Patterson BouleVard, Bristol, PennsylVania 19007, Matière et Systèmes Complexes (MSC), UMR 7057 CNRS, UniVersité Denis Diderot Paris-VII, Bâtiment Condorcet, 10 rue Alice Domon et Léonie Duquet, 75205 Paris, France, Institut Laue LangeVin, 6 rue Jules Horowitz, F-38042 Grenoble Cedex 9, France, and Centre de Recherche Paul Pascal (CRPP), CNRS, UniVersité Bordeaux 1, 33600 Pessac, France

Sensitive High Frequency AC Susceptometry in Magnetic Nanoparticle Applications

We report on the development of a sensitive high frequency susceptometer capable of measuring in the frequency range from 25 kHz up to 10 MHz with a volume susceptibility sensitivity of 3.5×l0−5 at 100 kHz corresponding to about 0.3% of the measured AC susceptibility. In combination with the previous reported DynoMag system capable of measuring dynamic magnetic properties in the range from 1 Hz to 200 kHz we are thus able to measure dynamic magnetic properties between 1 Hz to 10 MHz with high magnetic sensitivity. We will show AC susceptometry applications and results within the fields of magnetic hyperthermia and dynamic magnetic characterization of magnetic nanoparticle system with different particle sizes and magnetic properties.

Universal scattering behavior of coassembled nanoparticle-polymer clusters.

Water-soluble clusters made from 7-nm inorganic nanoparticles have been investigated by small-angle neutron scattering. The internal structure factor of the clusters was derived and exhibited a universal behavior as evidenced by a correlation hole at intermediate wave vectors. Reverse Monte Carlo calculations were performed to adjust the data and provided an accurate description of the clusters in terms of interparticle distance and volume fraction. Additional parameters influencing the microstructure were also investigated, including the nature and thickness of the nanoparticle adlayer.