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).
Angew Chem Int Ed Engl. 2014 Feb 10;53(7):1997-2001. doi: 10.1002/anie.201309985. Epub 2014 Jan 20.
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.
RNA 干扰 (RNAi) 是一种由 RNA 诱导的沉默复合物 (RISC) 控制的 RNA 依赖性基因沉默方法。在此，我们提出了一种合成的 RISC 模拟纳米复合物，它可以以序列特异性的方式主动切割其靶 RNA。该设计的纳米复合物具有高酶稳定性和高效的靶向细胞自我递送能力，能够选择性和有效地诱导基因沉默，而不会激活细胞因子。这些针对多药耐药性的纳米复合物不仅由于其纳米尺寸效应能够绕过 P 糖蛋白 (Pgp) 转运体，而且还能有效地抑制 Pgp 的表达，从而成功恢复 OVCAR8/ADR 细胞对 Pgp 可转运细胞毒药物的敏感性。这种纳米复合物方法具有功能基因组学和癌症治疗的潜力。
