CNRS UMR 8203 Vectorologie et thérapeutiques anticancéreuses, 114 rue Edouard Vaillant, 94805 Villejuif Cedex, France.
J Mol Recognit. 2013 Jul;26(7):318-29. doi: 10.1002/jmr.2276.
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 biotin-streptavidin 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.
尤因肉瘤是一种罕见的、主要发生在儿童期的骨癌，其特征是染色体异常，称为 EWS/Fli-1，导致肿瘤的发生。在体内，通过递送至肿瘤细胞的小干扰 RNA（siRNA）相关纳米颗粒，可以特异性地抑制肿瘤生长。本研究旨在设计针对细胞膜糖蛋白 cd99 的靶向纳米颗粒，该蛋白在尤因肉瘤细胞中过度表达，以提高 siRNA 递送至肿瘤细胞的效率。将生物素化聚异丁基氰基丙烯酸酯纳米颗粒作为平台，通过生物素化配体和生物素-链霉亲和素偶联方法设计靶向纳米颗粒。在携带尤因肉瘤肿瘤模型的小鼠中进行系统给药后，对靶向纳米颗粒进行体内验证，以实现 siRNA 的靶向递送。与非靶向纳米颗粒仅实现 41%±9%的抑制率相比，将 siRNA 与 cd99 靶向纳米颗粒结合可使负责尤因肉瘤的基因表达抑制达到 78%±6%。
