siRNA associated with immunonanoparticles directed against cd99 antigen improves gene expression inhibitionin vivoin Ewing's sarcoma
Résumé
Ewing sarcoma is a rare, mostly pediatric bone cancer which presents a chromosome abnormality, called EWS/Fli-1, responsible for the development of the tumours. In vivo, tumour growth can be inhibited specifically by delivering siRNA associated with nanoparticles. The aim of the work was to design targeted nanoparticles against the cell membrane glycoprotein cd99 which is over expressed in Ewing sarcoma cells in order to improve siRNA delivery to tumour cells. Biotinylated poly(isobutylcyanoacrylate) nanoparticles were conceived as a platform to design targeted nanoparticles with biotinylated ligands and using the biotin-streptavidin coupling method. The targeted nanoparticles were validated in vivo for targeted delivery of siRNA after systemic administration to mice bearing a tumor model of the Ewing sarcoma. The expression of the gene responsible of Ewing sarcoma was inhibited at 78 ± 6 % by associating the siRNA with the cd99 targeted nanoparticles compared with an inhibition of only 41 ± 9 % achieved with the non targeted nanoparticles.
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