Arginine-grafted bioreducible poly(disulfide amine) for gene delivery systems.
Arginine-grafted bioreducible poly(disulfide amine) (ABP) polymer was synthesized for non-viral gene delivery systems. Its Mw was measured to be 4.45x10(3) Da/mole by FPLC-SEC and its PDI value was 1.49. ABP was able to retard pDNA from a weight ratio of 2 but ABP could not retard pDNA even at a weight ratio of 10 in the presence of DTT, showing that it can be biodegraded in reducing environment such as cytoplasm. ABP was examined to form positively charged nano-sized particles (<200 nm) with pDNA. ABP showed no significant cytotoxicity and greatly enhanced transfection efficiency in comparison with unmodified poly(cystaminebisacrylamide-diaminohexane) (poly(CBA-DAH)) and PEI25k in mammalian cells. The transfection efficiency of ABP was not much reduced even in the serum condition. Chloroquine treatment was not found to improve the transfection efficiency of ABP. The cellular uptake pattern of ABP polyplexes was almost similar with poly(CBA-DAH), suggesting that greatly enhanced transfection efficiency of ABP is not induced by its high cellular penetrating ability but may be mediated by other factors such as good nuclear localization ability.
Kim
Tae-il
TI
Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Ou
Mei
M
Lee
Minhyung
M
Kim
Sung Wan
SW
D000818:Animals; D001120:Arginine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D051379:Mice; D010316:Particle Size; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014162:Transfection
D001672:Biocompatible Materials; D011073:Polyamines; C534803:arginine-grafted bioreducible poly(disulfide amine)polymer; D001120:Arginine