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.
Bibliographical noteFunding Information:
This work was supported by grants from the Global Innovative Research Center (GiRC) program; ( 2012K1A1A2A01056095 ) of National Research Fund (NRF) of Korea ; and the Intramural Research Program (Theragnosis, Global RNAi Carrier Initiative) of KIST ( 2E25530 ).
- Dual-gene delivery
- Glycol chitosan
- Tumor targeted delivery
- siRNA polymer