期刊
BIOMATERIALS
卷 34, 期 13, 页码 3431-3438出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.01.053
关键词
Polypeptide micelle; DTX; siRNA; Co-delivery; Synergistic tumor therapy
资金
- National Natural Science Foundation of China [81071249, 81171446, 20905050]
- Guangdong Innovation Research Team Fund for Low-cost Healthcare Technologies (GIRTF-LCHT)
- Key Project of Science and Technology of Guangdong [2009A030301010]
- Shenzhen Science and Technology Program [JC201005260247A, CXB201005250029A, JCYJ20120615125829685]
- Chinese Academy of Sciences
Combination of two or more therapeutic strategies with different mechanisms can cooperatively impede tumor growth. Co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) within a single nanoparticle (NP) provides a rational strategy for combined cancer therapy. Here, we prepared polypeptide micelle nanoparticles (NPs) of a triblock copolymer poly(ethylene glycol)-b-poly(L-lysine)-b-poly(L-leucine) (PEG-PLL-PLLeu) to systemically codeliver docetaxel (DTX) and siRNA-Bcl-2 for an effective drug/gene vector. The hydrophobic PLLeu core entrapped with anticancer drugs, while the PLL polypeptide cationic backbone allowed for electrostatic interaction with the negatively charged siRNA. The resulting micelle NP exhibited very stable, good biocompatible and excellent passive targeted properties. The micelle complexes with siRNA-Bcl-2 effectively knocked down the expression of Bcl-2 mRNA and protein. Moreover, the co-delivery system of DTX and siRNA-Bcl-2 (DTX siRNA NPs) obviously down-regulation of the anti-apoptotic Bcl-2 gene and enhanced antitumor activity with a smaller dose of DTX, resulting the significantly inhibited tumor growth of MCF-7 xenograft murine model as compared to the individual siRNA and only DTX treatments. Our results demonstrated well-defined PEG-PLL-PLLeu polypeptide cationic micelles with the excellent synergistic effect of DTX and siRNA-Bcl-2 in combined cancer therapy. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据