title: PEG conjugated VEGF siRNA for anti-angiogenic gene therapy.
abstract: A novel siRNA delivery system based on polyelectrolyte complex (PEC) micelles was introduced in this study. Vascular endothelial growth factor (VEGF) siRNA was conjugated to poly(ethylene glycol) (PEG) via a disulfide linkage (siRNA-PEG). The siRNA-PEG conjugate could form PEC micelles by interacting with cationic polyethylenimine (PEI) as a core forming agent. The VEGF siRNA-PEG/PEI PEC micelles showed greater stability than naked VEGF siRNA against enzymatic degradation. Under a reductive condition similar to cytosolic environment, an intact form of siRNA was released from the siRNA-PEG conjugate by cleavage of the disulfide linkage. The VEGF siRNA-PEG/PEI PEC micelles effectively silenced VEGF gene expression in prostate carcinoma cells (PC-3) up to 96.5% under an optimized formulation condition. They also showed a far superior VEGF gene silencing effect than VEGF siRNA/PEI complexes even in the presence of serum. This study suggests that the siRNA delivery system using VEGF siRNA-PEG/PEI PEC micelles could be potentially applied to RNAi-based anti-angiogenic treatment of cancer in vivo.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Kim
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Tae Gwan
authors.initials: TG
authors.lastname: Park
mesh_terms: D001798:Blood Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D004220:Disulfides / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D008823:Micelles; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000628:therapy*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000628:therapy*; D034622:RNA Interference; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D001798:Blood Proteins; D004220:Disulfides; D008823:Micelles; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; C028210:monomethoxypolyethylene glycol; D005978:Glutathione