pH-sensitive cationic polymer gene delivery vehicle: N-Ac-poly(L-histidine)-graft-poly(L-lysine) comb shaped polymer.
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.
Benns
J M
JM
Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Choi
J S
JS
Mahato
R I
RI
Park
J S
JS
Kim
S W
SW
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D006639:Histidine / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008239:Lysine / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D010455:Peptides / Q000138:chemical synthesis*; D010957:Plasmids / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D011994:Recombinant Proteins / Q000096:biosynthesis; D055672:Static Electricity; D014162:Transfection / Q000379:methods*; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D004337:Drug Carriers; D010455:Peptides; D011108:Polymers; D011994:Recombinant Proteins; D006639:Histidine; D001616:beta-Galactosidase; D008239:Lysine