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.
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