Biomimetic RNA-silencing nanocomplexes: overcoming multidrug resistance in cancer cells.
Biomimetic RNA-silencing nanocomplexes: overcoming multidrug resistance in cancer cells.
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DOI：
10.1002/anie.201309985
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发表时间：
2014-02-10
期刊：
影响因子：
--
通讯作者：
Chen X
中科院分区：
文献类型：
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作者：
Wang Z;Wang Z;Liu D;Yan X;Wang F;Niu G;Yang M;Chen X
RNA干扰（RNAi）是由RNA诱导的沉默复合物（RISC）控制的RNA依赖性基因沉默方法。在这里，我们代表合成的RISC-MIMIC纳米复合物，可以以序列特异性的方式积极地裂解其靶RNA。具有较高的酶促稳定性和对靶细胞有效自传递的有效自传递，设计的纳米复合物可以选择性地诱导基因沉默而无需细胞因子激活。靶向多药耐药性的纳米复合物不仅能够绕过P-糖蛋白（PGP）转运蛋白，因此由于其纳米尺寸效应，还可以有效地抑制PGP表达，从而成功抑制OVCAR8/ADR对PGP的药物敏感性的成功恢复 - 可转移的细胞毒性剂。这种纳米复合方法具有功能性基因组学和癌症治疗的潜力。
RNA interference (RNAi) is an RNA-dependent gene silencing approach controlled by RNA-induced silencing complex (RISC). Here we represent a synthetic RISC-mimic nanocomplex, which can actively cleave its target RNA in a sequence-specific manner. With high enzymatic stability and efficient self-delivery to target cells, the designed nanocomplex can selectively and potently induce gene silencing without cytokine activation. The nanocomplexes targeting to multidrug resistance are able to not only bypass P-glycoprotein (Pgp) transporter due to their nano-size effect, but also effectively suppress the Pgp expression, thus resulting in successful restoration of drug sensitivity of OVCAR8/ADR cells to Pgp-transportable cytotoxic agents. This nanocomplex approach has the potential for both functional genomics and cancer therapy.