Synergistic Inhibition of Human Carcinoma Cell Growth via Co-Delivery of p53 Plasmid DNA and bcl-2 Antisense Oligodeoxyribonucleotide by Cholic Acid-modified Polyethylenimine.

Abstract

This study investigated the co-delivery of plasmid DNA and antisense oligodeoxyribonucleotide (AS ODN) into carcinoma cells by cholic acid-modified polyethylenimine (PEI-CA). PEI-CA/plasmid DNA and AS ODN complexes were formulated and evaluated for delivery of plasmid DNA and AS ODN in HeLa cells. The efficiency of co-delivery of plasmid DNA and AS ODN was evaluated by cell growth inhibition using p53 and bcl-2 AS ODN. AS ODN intracellular delivery and green fluorescent protein expression upon cellular transfection were greater than in cells treated with uncomplexed nucleic acids. Treatment of the cells with PEI-CA/p53 plasmid DNA and bcl-2 AS ODN complexes resulted in cell growth inhibition that was greater than that of either PEI-CA/p53 plasmid DNA complexes or PEI-CA/bcl-2 AS ODN complexes alone. The co-delivery of p53 plasmid DNA and bcl-2 AS ODN in PEI-CA complexes enhanced therapeutic activities of both p53 plasmid DNA and bcl-2 AS ODN.