title: Intracellular delivery of poly(ethylene glycol) conjugated antisense oligonucleotide using cationic lipids by formation of self-assembled polyelectrolyte complex micelles.
abstract: A polyelectrolyte complex (PEC) micelle-based antisense oligodeoxynucleotide (ODN) delivery system was designed to overcome intrinsic limitations of cationic lipid-mediated gene transfer. Cationic lipid (Lipofectamine, LF) and ODN conjugated poly(ethylene glycol) (PEG) were ionically complexed to form self-assembled spherical PEC micelles. They have a distinctive structural feature: a charge-neutralized core surrounded by highly flexible PEG corona. The PEC micelles could be visualized as a nano-sized sphere by atomic force microscopy (AFM). The DNA/LF PEC micelles exhibited far improved transfection efficiency compared to those of conventional lipoplex formulations (ODN/LF) in the presence of serum. They showed enhanced cellular uptake followed by rapid nuclear localization of ODN in human epithelial carcinoma (KB) cells. In addition, anti-proliferative activity of c-raf gene-directed antisense ODN was almost fully maintained in KB cells in the presence of serum.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Tae Gwan
authors.initials: TG
authors.lastname: Park
mesh_terms: D002412:Cations; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry*; D004573:Electrolytes; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D008823:Micelles; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D002412:Cations; D004337:Drug Carriers; D004573:Electrolytes; D008055:Lipids; D008081:Liposomes; D008823:Micelles; D016376:Oligonucleotides, Antisense; D011092:Polyethylene Glycols