Benns J M, Choi J S, Mahato R I, Park J S, Kim S W
Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Bioconjug Chem. 2000 Sep-Oct;11(5):637-45. doi: 10.1021/bc0000177.
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.
生物技术的进步推动了新型药物工程基因递送载体的发展。聚（L-组氨酸）（PLH）已被证明能在内体pH值下诱导膜融合，而聚赖氨酸（PLL）在多聚体形成方面有充分记录的功效。因此，通过将聚（L-组氨酸）接枝到聚（L-赖氨酸）（PLL）上合成了N-乙酰基聚（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多聚体颗粒。多聚体的平均粒径在117±6纳米至306±77纳米范围内。在与pDNA的所有等效重量比下，PLH-g-PLL基因载体在293T细胞中表现出比PLL更高的转染效率。加入氯喹作为溶酶体溶解剂可增强PLL和PLH-g-PLL基因载体的转染。与PLL相比，PLH-g-PLL增强了β-半乳糖苷酶的表达，但当加入氯喹时，其功效仍会增加。
