pH-Sensitive Cationic Polymer Gene Delivery Vehicle: N-Ac-poly(l-histidine)-graft-poly(l-lysine) Comb Shaped Polymer

Top Cited Papers
Publisher Website
Google Scholar
Abstract
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 β-galactosidase expression compared to PLL, but still increased in efficacy when chloroquine was included.