Molecular Strings Significantly Improved the Gene Transfection Efficiency of Polycations
Molecular Strings Significantly Improved the Gene Transfection Efficiency of Polycations
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分子链显着提高聚阳离子基因转染效率
DOI：
10.1021/jacs.8b05341
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发表时间：
2018-09-26
影响因子：
15
通讯作者：
Chen, Xuesi
中科院分区：
文献类型：
--
作者：
Fang, Huapan;Guo, Zhaopei;Chen, Xuesi
高转染效率和低细胞毒性是设计基因载体时需要考虑的两个关键因素。本文通过在聚赖氨酸主链上引入“分子链”RT（即对甲基磺酰精氨酸），制备了一种新型的多功能基因载体（PLL-RT）。RT串的引入使多阳离子基因载体与细胞膜或DNA形成多重相互作用，并采用α -螺旋构象，有利于增强基因转染。此外，RT链接枝到其他多聚阳离子上，如超支化的PEI25k和树状大分子PAMAM，也可以获得更高的转染效率和低的细胞毒性。此外，PLL-RT在体内具有明显的肿瘤抑制作用。本研究为构建高转染、低细胞毒性的新型基因载体提供了有效的策略。
High transfection efficiency and low cytotoxicity are the two key factors to be considered in the design of gene carriers. Herein, a novel and versatile gene carrier (PLL-RT) was prepared by introducing "molecular string" RT (i.e., p-toluylsulfonyl arginine) onto the polylysine backbone. The introduction of RT string contributed to the formation of multiple interactions between the polycationic gene carriers and cell membrane or DNA, as well as adopting alpha-helix conformation, all of which would be beneficial to enhance the gene transfection. In addition, RT string grafted onto other polycations such as hyperbranced PEI25k and dendrimer PAMAM could also acquire improved transfection efficiency and low cytotoxicity. Moreover, PLL-RT presented significant tumor inhibition effect in vivo. This work provided an effective strategy for constructing novel gene carriers with high transfection and low cytotoxicity.