Juliette Moreau

Bifunctional polypyridyl-Ru(II) complex grafted onto gadolinium-based nanoparticles for MR-imaging and photodynamic therapy

The synthesis, optical properties and efficiency of new multifunctional nanoparticles as theranostic (fluorescence/MRI/PDT) agents are described. They are based on a polysiloxane network and surrounded by gadolinium(III) chelates and ruthenium(II) complexes. The size of the nanoparticles is maintained under 5 nm in order to permit their efficient elimination from the body. Their potential use as a theranostic agent (PDT/MRI) is described. The magnetic properties of the nanoparticles are studied by relaxometry (r1 = 9.21 mM(-1) s(-1) at 40 MHz; r2/r1 = 1.14) and the signal enhancement is validated by the acquisition of phantoms on a 3 T MRI imager. The therapeutic potential for photodynamic therapy of the nanoparticles has been studied in vitro on HEK293 cells and an effective quantum yield of 0.33 for (1)O2 production has been determined in deuterated water.

Synthesis and Physicochemical Characterization of 1,4,7,10-Tetra (2-glutaryl)-1,4,7,10 Tetraazacyclododecane Lanthanide Complexes

To describe a new tetra-(carboxyethyl) derivative of Gd-DOTA called P730 Gd (1): Figure 1. P730 Gd is a precursor in the synthesis of new macromolecular MRI contrast agents. The inner sphere contribution to the relaxivity of gadolinium complexes is determined by the rotational correlation time of the complex R, the water residence time M in the first coordination shell and the electronic relaxation time S (2). Each of these main relaxometric parameters is influenced by the structural characteristics of the complexes. Consequently, the structural and the physicochemical properties of each P730 diastereoisomer have been studied by crystallography, NMR and luminescence. In order to avoid complex dissociation, new Gd3 chelates should be characterized by high thermodynamic stability and transmetallation inertness, therefore the thermodynamic stability constant of P730 Gd was determined and its stability in a model of transmetallation was assessed. MATERIALS AND METHODS

Synthesis and Characterization of PEGylated and Fluorinated Chitosans: Application to the Synthesis of Targeted Nanoparticles for Drug Delivery

To synthesize chitosan nanoparticles (CS NPs), ionic gelation is a very attractive method. It relies on the spontaneous supramolecular assembly of cationic CS with anionic compounds, which leads to nanohydrogels. To extend ionic gelation to functionalized CS, the assessment of CS degree of substitution (DSCS) is a key step. In this paper, we have developed a hyphenated strategy for functionalized CS characterization, based upon 1H, DOSY and, when relevant, 1D diffusion-filtered 19F NMR spectroscopies. For that, we have synthesized two series of water-soluble CS via amidation of CS amino groups with mPEG2000-COOH or fluorinated synthons (TFB-COOH). The aforementioned NMR techniques helped to discriminate between ungrafted and grafted synthons and finally to determine DSCS. According to DSCS values, the selection of CS-mPEG2000 or CS-TFB copolymers can be made to obtain, in the presence of hyaluronic acid (HA) and tripolyphosphate (TPP), CS-mPEG2000-TPP/HA or CS-TFB-TPP/HA nanohydrogels suitable for drug delivery.