Intracellular delivery of poly(ethylene glycol) conjugated antisense oligonucleotide using cationic lipids by formation of self-assembled polyelectrolyte complex micelles.
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.
Jeong
Ji Hoon
JH
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
Kim
Sun Hwa
SH
Kim
Sung Wan
SW
Park
Tae Gwan
TG
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*
D002412:Cations; D004337:Drug Carriers; D004573:Electrolytes; D008055:Lipids; D008081:Liposomes; D008823:Micelles; D016376:Oligonucleotides, Antisense; D011092:Polyethylene Glycols