Prostate cancer cell-specific VEGF siRNA delivery system using cell targeting peptide conjugated polyplexes

J Drug Target. 2009 May;17(4):311-7. doi: 10.1080/10611860902767232.

Abstract

A polymeric gene carrier was developed to deliver vascular endothelial growth factor (VEGF) small interfering RNA (siRNA) for prostate cancer cells in a target-specific manner. Prostate cancer-binding peptide (PCP) was conjugated with polyethylenimine (PEI) via a poly(ethylene glycol) (PEG) linker (PEI-PEG-PCP). The PEI-PEG-PCP conjugate could effectively condense siRNA to form stable polyelectrolyte complexes (polyplexes) with an average diameter of approximately 150 nm in an aqueous solution. VEGF siRNA/PEI-PEG-PCP polyplexes exhibited significantly higher VEGF inhibition efficiency than PCP-unmodified polycationic carriers (PEI-PEG or PEI) in human prostate carcinoma cells (PC-3 cells). The enhanced gene silencing activity of VEGF siRNA/PEI-PEG-PCP was maintained even under serum conditions, owing to the steric stabilization of the polyplexes with hydrophilic PEG grafts. Confocal microscopic studies revealed that the siRNA/PEI-PEG-PCP polyplexes were delivered into PC-3 cells in a PCP ligand-specific manner.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Gene Silencing*
  • Gene Targeting
  • Gene Transfer Techniques
  • Humans
  • Ligands
  • Male
  • Microscopy, Confocal
  • Polyethylene Glycols / chemistry
  • Polyethyleneimine / chemistry
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / therapy*
  • RNA, Small Interfering / administration & dosage*
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Ligands
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A
  • Polyethylene Glycols
  • Polyethyleneimine