Abstract

This study aimed to evaluate the co-delivery of cationic liposome/plasmid DNA complexes and cationic liposome/antisense oligodeoxyribonucleotide (AS ODN) complexes in HeLa human cervical carcinoma cells. Dimethyldioctadecyl ammonium bromide (DDAB): dioleoyl phosphatidylethanolamine (DOPE) liposome/plasmid DNA complexes, and DDAB:DOPE liposome/AS ODN complexes were formulated and characterized in terms of agarose gel electrophoretic mobility, particle size and zeta potential. The complexes were evaluated for delivery of pEGFP plasmid DNA and AS ODN in HeLa cells. Cell growth inhibition was evaluated using p53 plasmid DNA and bcl-2 AS ODN, by codelivery of DDAB:DOPE liposome/p53 plasmid DNA and DDAB:DOPE liposome/bcl-2 AS ODN complexes. The particle size of DDAB:DOPE liposome/plasmid DNA complexes, and DDAB:DOPE liposome/AS ODN complexes were 180.6±2.0 to 372.3±2.4 nm, and zeta potentials were -26.7±1.2 to +6.8±0.4 mV, respectively. The AS ODN uptake and green fluorescent protein (GFP) expression upon their co-delivery by DDAB:DOPE liposomes were both high. Treatment of the cells with the co-delivery of DDAB:DOPE liposome/p53 plasmid DNA complexes and DDAB:DOPE liposome/ bcl-2 AS ODN complexes inhibited cell growth to a greater degree than that with either DDAB:DOPE liposome/p53 plasmid DNA complexes or DDAB:DOPE liposome/bcl-2 AS ODN complexes alone. These data suggest that co-delivery of cationic liposome/p53 plasmid DNA and cationic liposome/bcl-2 AS ODN complexes is an effective strategy to achieve enhanced therapeutic activities.

Keywords: Antisense oligodeoxyribonucleotide, bcl-2, co-delivery, growth inhibition, liposome, plasmid DNA, p53.