Biomedical subjects
Publications and source records attributed to M Bessodes.
Lipidic glycosides with amino alkyl pendent groups were synthesized and evaluated for in vitro DNA transfection activity. The first representative of this new class of cationic lipids showed good gene delivery and low toxicity to HeLa and 3T3 cells.
We have developed new DNA complexing amphiphile based on Hoechst 33258 interaction with DNA grooves. The synthesis and physicochemical characterisation of lipid/DNA complexes, as compared to that of classical lipopolyamine for gene delivery, are described and discussed.
Various analogs of statine, a remarkable amino acid component of the protease inhibitor pepstatine, were synthesized and evaluated as tripeptide derivatives for their activity against cathepsin D and HIV-1 protease.
Cationic lipids are widely used for in vitro gene transfer due to their efficiency. The major challenges for the improvement of in vivo cationic lipid-mediated gene delivery reside in the design of more biocompatible lipoplexes mimicking viral-mediated gene delivery and in understanding the fate of the lipoplexes within the cells.
AIM allows imaging and quantification of all elements on a biological tissue section. However quantification is limited by physical parameters which are difficult to assess and which intervene for a given element in the relation between its concentration and the measured signal. Thus, to quantify iodine in thyroid follicles, an iodine standard was prepared. Homogeneity in its atomic iodine distribution was tested by surface and depth analyses. Then, a standard curve was generated to be used as a reference for quantification of iodine on histological preparation by AIM.
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Surface modification of cationic lipoplexes has been carried out by means of a postgrafting reaction. The original lipoplexes described comprise a cationic lipid, a neutral lipid, poly(ethylene glycol)-cholesterol (with or without a targeting ligand) and DNA. Modifying their surface via a chemical, postgrafting reaction did not alter their size (approximately 100 nm) nor their ability to compact DNA, but did give a reduced zeta potential (approximately 0 mV) to afford surface neutral particles. With the modified lipoplexes nonspecific NIH3T3 cell surface binding in vitro was inhibited. Intravenous injection of the neutralized lipoplexes in mice showed decreased accumulation of the particles in the lung as compared to PEGylated cationic lipoplexes. Tumor targeting was also achieved in vivo by the addition of an RGD-PEG-Cholesterol as a lipid-ligand in the postgrafted lipoplex formulation.