Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea.
College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
J Control Release. 2015 Dec 28;220(Pt B):631-41. doi: 10.1016/j.jconrel.2015.08.032. Epub 2015 Aug 23.
Cancer is a multifactorial disease which involves complex genetic mutation and dysregulation. Combinatorial RNAi technology and concurrent multiple gene silencing are expected to provide advanced strategies for effective cancer therapy, but a safe and effective carrier system is a prerequisite to successful siRNA delivery in vivo. We previously developed an effective tumor-targeting siRNA delivery system for in vivo application. In response to the success of this development, herein we present a dual-gene targeted siRNA and its delivery system, to achieve synergistic effects in cancer therapy. Two different sequences of siRNA were chemically modified to be randomly copolymerized in a single backbone of siRNA polymer (Dual-poly-siRNA), and the resulting Dual-poly-siRNA was incorporated into tumor-homing glycol chitosan nanoparticles. Based on the stability in serum and delivery in a tumor-targeted manner, intravenously administered Dual-poly-siRNA carrying glycol chitosan nanoparticles (Dual-NP) demonstrated successful dual-gene silencing in tumors. Notably, co-delivery of VEGF and Bcl-2 targeting siRNA led to more effective cancer therapy for convenient application.
癌症是一种多因素疾病，涉及复杂的基因突变和失调。组合 RNAi 技术和同时多个基因沉默有望为有效的癌症治疗提供先进的策略，但安全有效的载体系统是体内成功递送 siRNA 的前提。我们之前开发了一种有效的肿瘤靶向 siRNA 递药系统，用于体内应用。针对这一开发的成功，我们在此提出了一种双基因靶向 siRNA 及其递药系统，以实现癌症治疗的协同效应。两条不同序列的 siRNA 经化学修饰，随机共聚于 siRNA 聚合物的单个主链上（双聚 siRNA），并将所得的双聚 siRNA 整合到肿瘤归巢性的聚乙二醇化壳聚糖纳米颗粒中。基于在血清中的稳定性和肿瘤靶向递药方式，静脉内给予携带聚乙二醇化壳聚糖纳米颗粒的双聚 siRNA（双 NP）可在肿瘤中成功实现双基因沉默。值得注意的是，共递送 VEGF 和 Bcl-2 靶向 siRNA 可更有效地进行癌症治疗，便于应用。
