Co-delivery of paclitaxel and anti-survivin siRNA via redox-sensitive oligopeptide liposomes for the synergistic treatment of breast cancer and metastasis

Publication date: 30 August 2017 Source:International Journal of Pharmaceutics, Volume 529, Issues 1–2 Author(s): Xinyan Chen, Yidi Zhang, Chunming Tang, Chunli Tian, Qiong Sun, Zhigui Su, Lingjing Xue, Yifan Yin, Caoyun Ju, Can Zhang The overexpression of survivin in breast cancer cells is an important factor of paclitaxel (PTX) resistance in breast cancer. To overcome PTX resistance and improve the antitumor effect of PTX, we developed a novel liposome-based nanosystem (PTX/siRNA/SS-L), composed of a redox-sensitive cationic oligopeptide lipid (LHSSG2C14) with a proton sponge effect, natural soybean phosphatidylcholine (SPC), and cholesterol for co-delivery of PTX and anti-survivin siRNA, which could specifically downregulate survivin overexpression. PTX/siRNA/SS-L exhibited high encapsulation efficiency and rapid redox-responsive release of both PTX and siRNA. Moreover, in vitro studies on the 4T1 breast cancer cells revealed that PTX/siRNA/SS-L offered significant advantages over other experimental groups, such as higher cellular uptake, successful endolysosomal escape, reduced survivin expression, the lowest cell viability and wound healing rate, as well as the highest apoptosis rate. In particular, in vivo evaluation of 4T1 tumor-bearing mice showed that PTX/siRNA/SS-L had lower toxicity and induced a synergistic inhibitory effect on tumor growth and pulmonary metastasis. Collectively, the collaboration of anti-survivin siRNA and PTX via redox-sensitive ol...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research