title: Prostate cancer cell-specific VEGF siRNA delivery system using cell targeting peptide conjugated polyplexes.
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.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Kim
authors.forename: Soo Hyeon
authors.initials: SH
authors.lastname: Lee
authors.forename: Huayu
authors.initials: H
authors.lastname: Tian
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
authors.forename: Tae Gwan
authors.initials: TG
authors.lastname: Park
mesh_terms: D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D020868:Gene Silencing; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D006801:Humans; D008024:Ligands; D008297:Male; D018613:Microscopy, Confocal; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000235:genetics / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D008024:Ligands; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D011092:Polyethylene Glycols; D011094:Polyethyleneimine