RNase non-sensitive and endocytosis independent siRNA delivery system: delivery of siRNA into tumor cells and high efficiency induction of apoptosis
RNase non-sensitive and endocytosis independent siRNA delivery system: delivery of siRNA into tumor cells and high efficiency induction of apoptosis
复制标题
RNase不敏感且不依赖内吞作用的siRNA递送系统：将siRNA递送至肿瘤细胞并高效诱导细胞凋亡
DOI：
10.1039/c3nr01183f
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发表时间：
2013-01-01
期刊：
影响因子：
6.7
通讯作者：
Gao, Xueyun
中科院分区：
文献类型：
--
作者：
Jiang, Xinglu;Wang, Guobao;Gao, Xueyun
迄今为止，RNA酶降解和内体/溶酶体捕获仍然是基于siRNA的分子治疗的严重问题，尽管已经尝试了不同种类的递送制剂。在本报告中，细胞穿透肽（CPP，包括带正电荷的部分，线性部分，和疏水性部分）和单壁碳纳米管（SWCNT）通过一种简单的方法一起应用，作为siRNA的传递系统。siRNA首先通过静电力与CPP的带正电荷的片段形成复合物，并且siRNA-CPP通过疏水相互作用进一步涂覆SWCNT的表面。该siRNA递送系统对RNase不敏感，并且可以避免体外内体/溶酶体捕获。当在Hela细胞中研究这种siRNA递送系统时，在98%的Hela细胞中观察到siRNA摄取，并且超过70%的哺乳动物雷帕霉素靶蛋白（mTOR）的mRNA被敲低，从而以显著的规模触发细胞凋亡。我们的siRNA递送系统易于操作并且对培养的细胞是良性的，为将siRNA递送到细胞胞质溶胶中并切割其中的靶mRNA提供了非常有效的方法。
To date, RNase degradation and endosome/lysosome trapping are still serious problems for siRNA-based molecular therapy, although different kinds of delivery formulations have been tried. In this report, a cell penetrating peptide (CPP, including a positively charged segment, a linear segment, and a hydrophobic segment) and a single wall carbon nanotube (SWCNT) are applied together by a simple method to act as a siRNA delivery system. The siRNAs first form a complex with the positively charged segment of CPP via electrostatic forces, and the siRNA-CPP further coats the surface of the SWCNT via hydrophobic interactions. This siRNA delivery system is non-sensitive to RNase and can avoid endosome/lysosome trapping in vitro. When this siRNA delivery system is studied in Hela cells, siRNA uptake was observed in 98% Hela cells, and over 70% mRNA of mammalian target of rapamycin (mTOR) is knocked down, triggering cell apoptosis on a significant scale. Our siRNA delivery system is easy to handle and benign to cultured cells, providing a very efficient approach for the delivery of siRNA into the cell cytosol and cleaving the target mRNA therein.