Intracellular siRNA delivery system using polyelectrolyte complex micelles prepared from VEGF siRNA-PEG conjugate and cationic fusogenic peptide

Biochem Biophys Res Commun. 2007 Jun 1;357(2):511-6. doi: 10.1016/j.bbrc.2007.03.185. Epub 2007 Apr 9.

Abstract

To develop a small interfering RNA (siRNA) delivery system with low cytotoxicity and high transfection efficiency, siRNA was conjugated to poly(ethylene glycol) via a disulfide linkage (siRNA-PEG) to prepare polyelectrolyte complex micelles (PECMs) by condensing with a cationic fusogenic peptide (KALA). The siRNA-PEG conjugate exhibited enhanced resistance to degradation from nucleases. Anionic siRNA-PEG conjugate and cationic KALA, when mixed in an aqueous phase, spontaneously formed nano-sized PECMs (<200nm) that have an inner core of charge neutralized siRNA/KALA complex surrounded by a PEG corona. Vascular endothelial growth factor (VEGF) siRNA was used to demonstrate VEGF sequence-specific gene inhibition in prostate carcinoma cells (PC-3 cells). The extent of gene silencing was gradually increased with increasing nitrogen to phosphate (N/P) ratio and the concentration of siRNA-PEG/KALA PECMs. These results suggest that the formulation of siRNA-PEG/KALA PECMs could be widely applied for intracellular delivery of various therapeutic siRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials / chemistry
  • Cell Line, Tumor
  • Drug Delivery Systems / methods*
  • Electrolytes / chemistry
  • Gene Silencing
  • Humans
  • Liposomes / chemistry
  • Male
  • Micelles
  • Polyethylene Glycols / chemistry*
  • Prostatic Neoplasms / physiopathology*
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / pharmacokinetics*
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Biocompatible Materials
  • Electrolytes
  • Liposomes
  • Micelles
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A
  • Polyethylene Glycols