Electroneutralized Amphiphilic Triblock Copolymer with a Peptide Dendron for Efficient Muscular Gene Delivery
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- 作者：Linyu Pu ; Yanyan Geng ; Sijia Liu ; Jianlin Chen ; Kui Luo ; Gang Wang ; Zhongwei Gu
- 刊名：ACS Applied Materials & Interfaces
- 出版年：2014
- 出版时间：September 10, 2014
- 年：2014
- 卷：6
- 期：17
- 页码：15344-15351
- 全文大小：429K
- ISSN：1944-8252
文摘
Hydrophilic鈥揾ydrophobic鈥揾ydrophilic triblock copolymers, such as Pluronic L64, P85, and P105, have attracted more attention due to their enhancement in muscular gene delivery. In the present study, a new kind of electroneutralized triblock copolymer, LPL, dendron G2(l-lysine-Boc)-PEG2k-dendron G2(l-lysine-Boc), was designed and investigated. This hydrophobic鈥揾ydrophilic鈥揾ydrophobic copolymer is composed of a structure reverse to that of L64, one of the most effective materials for intramuscular gene delivery so far. Our results showed that LPL exhibited good in vivo biocompatibility after intramuscular and intravenous administration. LPL mediated higher reporter gene expression than L64 in assays of 尾-galactosidase (LacZ), luciferase, and fluorescent protein E2-Crimson. Furthermore, LPL-mediated mouse growth hormone expression significantly accelerated mouse growth within the first 10 days. Altogether, LPL-mediated gene expression in skeletal muscle exhibits the potential of successful gene therapy. The current study also presented an innovative way to design and construct new electroneutralized triblock copolymers for safe and effective intramuscular gene delivery.