siRNA associated with immunonanoparticles directed against cd99 antigen improves gene expression inhibition in vivo in Ewing's sarcoma

作者：Ramon A L; Bertrand J R; de Martimprey H; Bernard G; Ponchel G; Malvy C; Vauthier C^*

来源：Journal of Molecular Recognition, 2013, 26(7): 318-329.

DOI：10.1002/jmr.2276

• Ewing's sarcoma
• siRNA
• immunonanoparticles
• poly(alkylcyanoacrylate) nanoparticles
• chitosan

Ewing's sarcoma is a rare, mostly pediatric bone cancer that presents a chromosome abnormality called EWS/Fli-1, responsible for the development of the tumor. In vivo, tumor growth can be inhibited specifically by delivering small interfering RNA (siRNA) associated with nanoparticles. The aim of the work was to design targeted nanoparticles against the cell membrane glycoprotein cd99, which is overexpressed in Ewing's sarcoma cells to improve siRNA delivery to tumor cells. Biotinylated poly(isobutylcyanoacrylate) nanoparticles were conceived as a platform to design targeted nanoparticles with biotinylated ligands and using the biotinstreptavidin coupling method. The targeted nanoparticles were validated in vivo for the targeted delivery of siRNA after systemic administration to mice bearing a tumor model of the Ewing's sarcoma. The expression of the gene responsible of Ewing's 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 nontargeted nanoparticles.

• 出版日期2013-7