Biomimetic RNA-silencing nanocomplexes: overcoming multidrug resistance in cancer cells

Angew Chem Int Ed Engl. 2014 Feb 10;53(7):1997-2001. doi: 10.1002/anie.201309985. Epub 2014 Jan 20.

Abstract

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.

Keywords: biomimetics; drug design; gene regulation; gold; nanoparticles.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomimetic Materials / chemistry*
  • Biomimetic Materials / pharmacology
  • Cell Line, Tumor
  • Drug Design
  • Drug Resistance, Multiple
  • Gene Silencing
  • Gold / administration & dosage
  • Gold / chemistry*
  • Humans
  • Metal Nanoparticles / administration & dosage
  • Metal Nanoparticles / chemistry*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • RNA Interference
  • RNA-Induced Silencing Complex / chemistry*
  • RNA-Induced Silencing Complex / metabolism

Substances

  • RNA-Induced Silencing Complex
  • Gold