Biomimetic RNA-silencing nanocomplexes: overcoming multidrug resistance in cancer cells.
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.
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bio-engineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD 20892 (USA); Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361005 (China).
Zhongliang
Z
Wang
Zhe
Z
Wang
Dingbin
D
Liu
Xuefeng
X
Yan
Fu
F
Wang
Gang
G
Niu
Min
M
Yang
Xiaoyuan
X
Chen
D040761:Biomimetic Materials / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D015195:Drug Design; D018432:Drug Resistance, Multiple; D020868:Gene Silencing; D006046:Gold / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D034622:RNA Interference; D034743:RNA-Induced Silencing Complex / Q000737:chemistry* / Q000378:metabolism
D034743:RNA-Induced Silencing Complex; D006046:Gold
biomimetics; drug design; gene regulation; gold; nanoparticles