Target-specific gene silencing of layer-by-layer assembled gold-cysteamine/siRNA/PEI/HA nanocomplex

ACS Nano. 2011 Aug 23;5(8):6138-47. doi: 10.1021/nn2017793. Epub 2011 Jul 8.


Target-specific intracellular delivery of small interfering RNA (siRNA) is regarded as one of the most important technologies for the development of siRNA therapeutics. In this work, a cysteamine modified gold nanoparticles (AuCM)/siRNA/polyethyleneimine (PEI)/hyaluronic acid (HA) complex was successfully developed using a layer-by-layer method for target-specific intracellular delivery of siRNA by HA receptor mediated endocytosis. Atomic force microscopic and zeta potential analyses confirmed the formation of a AuCM/siRNA/PEI/HA complex having a particle size of ca. 37.3 nm and a negative surface charge of ca. -12 mV. With a negligible cytotoxicity, AuCM/siRNA/PEI/HA complex showed an excellent target-specific gene silencing efficiency of ca. 70% in the presence of 50 vol % serum, which was statistically much higher than that of siRNA/Lipofectamine 2000 complex. In the competitive binding tests with free HA, dark-field bioimaging and inductively coupled plasma-atomic emission spectroscopy confirmed the target-specific intracellular delivery of AuCM/siRNA/PEI/HA complex to B16F1 cells with HA receptors. Moreover, the systemic delivery of AuCM/siRNA/PEI/HA complex using apolipoprotein B (ApoB) siRNA as a model drug resulted in a significantly reduced ApoB mRNA level in the liver tissue. Taken together, AuCM/siRNA/PEI/HA complex was thought to be developed as target-specific siRNA therapeutics for the systemic treatment of various liver diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins B / deficiency
  • Apolipoproteins B / genetics
  • Base Sequence
  • Cell Line, Tumor
  • Cysteamine / chemistry*
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism
  • Endocytosis
  • Gene Silencing*
  • Gold / chemistry*
  • Hyaluronic Acid / chemistry*
  • Intracellular Space / metabolism
  • Liver Diseases / genetics
  • Liver Diseases / metabolism
  • Liver Diseases / therapy
  • Mice
  • Models, Molecular
  • Molecular Conformation
  • Molecular Imaging
  • Nanostructures / chemistry
  • Nanotechnology / methods*
  • Polyethyleneimine / chemistry*
  • RNA, Small Interfering / chemistry*
  • RNA, Small Interfering / genetics


  • Apolipoproteins B
  • Drug Carriers
  • RNA, Small Interfering
  • Cysteamine
  • Gold
  • Polyethyleneimine
  • Hyaluronic Acid