Journal
MACROMOLECULAR BIOSCIENCE
Volume 10, Issue 8, Pages 898-905Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.200900482
Keywords
biodegradability; bioreducible cationic polymer; cytoplasmic localization; nanoparticles; polyelectrolyte complexes; siRNA delivery; polyelectrolytes
Funding
- National Institutes of Health [CA107070]
- Ministry for Health, Welfare & Family Affairs, Republic of Korea [A085136]
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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.
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