Université de Paris-Sud-11, UMR CNRS 8612, 5 rue J.B. Clément, 92296, Châtenay-Malabry, France.
Pharm Res. 2010 Mar;27(3):498-509. doi: 10.1007/s11095-009-0043-8. Epub 2010 Jan 20.
Development of efficient in vivo delivery nanodevices remains a major challenge to achieve clinical application of siRNA. The present study refers to the conception of core-shell nanoparticles aiming to make possible intravenous administration of chemically unmodified siRNA oriented towards the junction oncogene of the papillary thyroid carcinoma.
Nanoparticles were prepared by redox radical emulsion polymerization of isobutylcyanoacrylate and isohexylcyanoacrylate with chitosan. The loading of the nanoparticles with siRNA was achieved by adsorption. The biological activity of the siRNA-loaded nanoparticles was assessed on mice bearing a papillary thyroid carcinoma after intratumoral and intravenous administration.
Chitosan-coated nanoparticles with a diameter of 60 nm were obtained by adding 3% pluronic in the preparation medium. siRNA were associated with the nanoparticles by surface adsorption. In vivo, the antisense siRNA associated with the nanoparticles lead to a strong antitumoral activity. The tumor growth was almost stopped after intravenous injection of the antisense siRNA-loaded nanoparticles, while in all control experiments, the tumor size was increased by at least 10 times.
This work showed that poly(alkylcyanoacrylate) nanoparticles coated with chitosan are suitable carriers to achieve in vivo delivery of active siRNA to tumor including after systemic administration.
开发高效的体内递药纳米器件仍然是实现 siRNA 临床应用的主要挑战。本研究提出了核壳纳米粒子的概念，旨在实现针对甲状腺乳头状癌连接癌基因的化学未修饰 siRNA 的静脉给药。
采用异丁基氰基丙烯酸酯和异己基氰基丙烯酸酯与壳聚糖的氧化还原自由基乳液聚合制备纳米粒子。通过吸附作用将 siRNA 载入纳米粒子。在荷有甲状腺乳头状癌的小鼠中进行瘤内和静脉给药后，评估载有 siRNA 的纳米粒子的生物活性。
在制备介质中添加 3%的 pluronic 可获得直径为 60nm 的壳聚糖包覆纳米粒子。siRNA 通过表面吸附与纳米粒子结合。在体内，与纳米粒子结合的反义 siRNA 导致强烈的抗肿瘤活性。静脉注射载有反义 siRNA 的纳米粒子后，肿瘤生长几乎停止，而在所有对照实验中，肿瘤大小至少增加了 10 倍。
这项工作表明，壳聚糖包覆的聚（烷基氰基丙烯酸酯）纳米粒子是实现活性 siRNA 体内递送至肿瘤（包括系统给药后）的合适载体。
