Injectable Polyplex Hydrogel for Localized and Long-Term Delivery of siRNA
Injectable Polyplex Hydrogel for Localized and Long-Term Delivery of siRNA
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DOI：
10.1021/nn300842a
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发表时间：
2012-07-01
期刊：
影响因子：
17.1
通讯作者：
Song, Soo-Chang
中科院分区：
文献类型：
--
作者：
Kim, Young-Min;Park, Mi-Ran;Song, Soo-Chang
在这里，我们描述了一个概念，使用具有热敏性和生物降解性的可注射复合物水凝胶的局部和长期交付的短干扰RNA（siRNA）。我们制备了一种低分子量聚乙烯亚胺-聚（有机腈）共轭物，作为具有可裂解酯键的热敏阳离子聚合物。缀合物与siRNA形成约100 nm大小的复合物，并且复合物溶液在体温下通过疏水相互作用变成复合物水凝胶。我们将含有细胞周期蛋白B1（一种控制细胞周期的必需蛋白）siRNA的复合物水凝胶注射到肿瘤异种移植模型中。通过溶解和降解从复合物水凝胶中缓慢释放复合物，允许仅用单次注射通过细胞周期蛋白B1基因沉默4周的体内抗肿瘤作用。
Here, we describe a concept for localized and long-term delivery of short interfering RNA (siRNA) using an injectable polyplex hydrogel possessing thermosensitivity and biodegradability properties. We prepared a low molecular weight polyethyleneimine-poly(organophosphazene) conjugate as a thermosensitive and cationic polymer that has a cleavable ester linkage. The conjugates formed about 100 nm sized polyplexes with siRNAs, and the polyplex solution turned into a polyplex hydrogel at body temperature via a hydrophobic interaction. We injected the polyplex hydrogel with siRNA of cyclin B1, an essential protein for controlling the cell cycle, into the tumor xenograft model. Polyplexes were slowly released from the polyplex hydrogel by dissolution and degradation, allowing an in vivo antitumor effect via cyclin B1 gene silencing for 4 weeks with only a single injection.