Self-Assembled Cationic Micelles Based on PEG-PLL-PLLeu Hybrid Polypeptides as Highly Effective Gene Vectors

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• 作者：Jizhe Deng ; Ningning Gao ; Yanan Wang ; Huqiang Yi ; Shengtao Fang ; Yifan Ma ; Lintao Cai
• 刊名：Biomacromolecules
• 出版年：2012
• 出版时间：November 12, 2012
• 年：2012
• 卷：13
• 期：11
• 页码：3795-3804
• 全文大小：577K
• 年卷期：v.13,no.11(November 12, 2012)
• ISSN：1526-4602

文摘

Developing safe and effective nonviral gene vector is highly crucial for successful gene therapy. In the present study, we designed a series of biodegradable micelles based on hybrid polypeptide copolymers of poly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-leucine) (PEG-PLL-PLLeu) for efficient gene delivery. A group of amphiphilic PEG-PLL-PLLeu hybrid polypeptide copolymers were synthesized by ring-opening polymerization of N-carboxyanhydride, and the chemical structure of each copolymer was characterized by ¹H NMR and FT-IR spectroscopy measurement. The PEG-PLL-PLLeu micelles were positively charged with tunable sizes ranging from 40 to 90 nm depending on the length of PLL and PLLeu segment. Compared with PEG-PLL copolymers, PEG-PLL-PLLeu micelles demonstrated significantly higher transfection efficiency and less cytotoxicity. Furthermore, the transfection efficiency and biocompatibility of the micelles can be simultaneously improved by tuning the length of PLL and PLLeu segments. The transfection efficiency of PEG-PLL-PLLeu micelles in vivo was two to three times higher than that of PEI_25k, which was attributable to their capability of promoting DNA condensation and cell internalization as well as successful lysosome escape. Hence well-defined PEG-PLL-PLLeu micelles would serve as highly effective nonviral vectors for in vivo gene delivery.