Reductive Degradation Behavior of Bioreducible Poly(disulfide amine) for Enhancing SiRNA Efficiency
Reductive Degradation Behavior of Bioreducible Poly(disulfide amine) for Enhancing SiRNA Efficiency
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DOI：
10.1002/mabi.200900482
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发表时间：
2010-08-11
影响因子：
4.6
通讯作者：
Kim, Sung Wan
中科院分区：
文献类型：
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作者：
Kim, Sun Hwa;Ou, Mei;Kim, Sung Wan
通过 CBA 与 DAH 单体的 Michael 型加成反应合成了聚合物主链上含有重复二硫键的生物可还原阳离子聚合物聚 (CBA-DAH)。 Poly(CBA-DAH) 可以通过与水相中 siRNA 的静电相互作用自发形成纳米级聚电解质复合物。由于聚合物中二硫键的分解，这些纳米颗粒在还原性细胞质环境下迅速降解，随后将 siRNA 货物释放到发生 RNAi 的细胞质中。 Poly(CBA-DAH)/siRNA 复合物的还原降解行为更有可能通过增强 siRNA 分子的细胞质定位来增加 RNAi 活性。由于其还原降解特性，Poly(CBA-DAH) 作为基因载体可能具有巨大的潜力，特别是对于 siRNA 的治疗应用。
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.