Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 529, Issue 1-2, Pages 102-115Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2017.06.071
Keywords
Co-delivery; Paclitaxel; Anti-survivin siRNA; Redox-sensitive oligopeptide liposomes; Breast cancer; Synergistic inhibition
Categories
Funding
- National Natural Science Foundation of China [81273468, 81473153, 81503003, 81503006]
- National Basic Research Program of China [2015CB755500]
- Natural Science Foundation of Jiangsu Province of China [BK20140672, BK20150698]
- Fundamental Research Funds for the Central Universities of China [2632017ZD06, 2015PY014]
- 111 Project from the Ministry of Education of China
- 111 Project from the State Administration of Foreign Expert Affairs of China [111-2-07]
- National Training Program of Innovation and Entrepreneurship for Undergraduates [201610316098]
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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 (LHSSG2C(14)) 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 redoxresponsive 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 antisurvivin siRNA and PTX via redox-sensitive oligopeptide liposomes provides a promising strategy for the treatment of breast cancer and metastasis. (C) 2017 Elsevier B.V. All rights reserved.
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