Reductive degradation behavior of bioreducible poly(disulfide amine) for enhancing SiRNA efficiency.
Bioreducible cationic polymer poly(CBA-DAH) containing repeated disulfide linkages on the polymer backbone was synthesized through Michael-type polyadditions of CBA to DAH monomers. Poly(CBA-DAH) could spontaneously form nanoscale polyelectrolyte complexes through electrostatic interactions with siRNA in an aqueous phase. These nanoparticles were rapidly degraded under the reductive cytoplasmic environment with subsequently releasing the siRNA cargo into the cytoplasm where RNAi takes place, as a result of the breakdown of disulfide bonds in the polymers. The reductive degradation behavior of the poly(CBA-DAH)/siRNA polyplexes is more likely to increase RNAi activity with enhancing the cytoplasmic localization of siRNA molecules. Poly(CBA-DAH) may have great potential as a gene carrier especially for therapeutic applications of siRNAs owing to the reductive degradation characteristics.
Kim
Sun Hwa
SH
Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Ou
Mei
M
Bull
David A
DA
Kim
Sung Wan
SW
D000180:Acrylic Resins / Q000737:chemistry*; D001672:Biocompatible Materials; D045744:Cell Line, Tumor; D004220:Disulfides / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D034741:RNA, Small Interfering / Q000235:genetics*; D014162:Transfection
D000180:Acrylic Resins; D001672:Biocompatible Materials; D004220:Disulfides; D034741:RNA, Small Interfering