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Biomimetic RNA‐Silencing Nanocomplexes: Overcoming Multidrug Resistance in Cancer Cells
Author(s) -
Wang Zhongliang,
Wang Zhe,
Liu Dingbin,
Yan Xuefeng,
Wang Fu,
Niu Gang,
Yang Min,
Chen Xiaoyuan
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201309985
Subject(s) - gene silencing , rna interference , small interfering rna , multiple drug resistance , rna induced silencing complex , rna , rna silencing , rna induced transcriptional silencing , chemistry , cancer cell , microbiology and biotechnology , trans acting sirna , biology , computational biology , gene , drug resistance , cancer , biochemistry , genetics
RNA interference (RNAi) is an RNA‐dependent gene silencing approach controlled by an RNA‐induced silencing complex (RISC). Herein, we present 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. These nanocomplexes, which target multidrug resistance, are not only able to bypass the P‐glycoprotein (Pgp) transporter, due to their nano‐size effect, but also effectively suppress 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.