pH-sensitive cationic polymer gene delivery vehicle:: N-Ac-poly(L-histidine)-graft-poly(L-lysine) comb shaped polymer
pH-sensitive cationic polymer gene delivery vehicle:: N-Ac-poly(L-histidine)-graft-poly(L-lysine) comb shaped polymer
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DOI：
10.1021/bc0000177
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发表时间：
2000-09-01
影响因子：
4.7
通讯作者：
Kim, SW
中科院分区：
文献类型：
--
作者：
Benns, JM;Choi, JS;Kim, SW
先进的生物技术刺激了新的药物工程基因载体的发展。聚（L-组氨酸）{PLH}已显示在内体pH值下诱导膜融合，而PLL在多聚物形成中具有充分记载的功效。因此，通过将聚（L-组氨酸）接枝到聚（L-赖氨酸）{PLL}上，合成了N-Ac-聚（L-组氨酸）接枝-聚（L-赖氨酸）{PLH-g-PLL}。PLH-g-PLL通过与质粒DNA {pDNA}的静电相互作用形成聚合物颗粒。聚合复合物的平均粒度在117 +/-6nm至306 +/-77nm的范围内。PLH-g-PLL基因载体在与pDNA的所有当量比下在293 T细胞中表现出比PLL更高的转染效率。氯喹作为内体溶解剂的加入增强了PLL和PLH-g-PLL基因载体的转染。与PLL相比，PLH-g-PLL增强β-半乳糖苷酶表达，但当包括氯喹时仍增加功效。
Advancing biotechnology spurs the development of new pharmaceutically engineered gene delivery vehicles. Poly(L-histidine) {PLH} has been shown to induce membrane fusion at endosomal pH values, whereas PLL has a well documented efficacy in polyplex formation. Therefore, N-Ac-poly(L-histidine)graft-poly(L-lysine) {PLH-g-PLL} was synthesized by grafting poly(L-histidine) to poly(L-lysine) {PLL}. PLH-g-PLL formed polyplex particles by electrostatic interactions with plasmid DNA {pDNA}. The mean particle size of the polyplexes was in the range of 117 +/- 6 nm to 306 +/- 77 nm. PLH-g-PLL gene carrier demonstrated higher transfection efficacy in 293T cells than PLL at all equivalent weight ratios with pDNA. The inclusion of chloroquine as an endosomolytic agent enhanced transfection for both PLL and PLH-g-PLL gene carriers. PLH-g-PLL enhanced beta-galactosidase expression compared to PLL, but still increased in efficacy when chloroquine was included.