Liposomal Targeting of Bcl-2 Antisense Oligonucleotides with Enhanced Stability into Human Myeloma Cell Lines

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Abstract
Cationic liposomes improve the delivery of antisense oligonucleotides (ODNs) into cells. However, there is marked variability in the cellular uptake of ODNs into different cell lines. We used liposomes containing dimethyloctadecylammonium bromide (DDAB) and dioleoylphosphatidylethanolamine (DOPE) to increase the delivery of phosphodiester ODNs into four different myeloma cell lines. The delivery by cationic liposomes increased the delivery of bcl-2 antisense ODNs by a factor of 9 to 45 as compared to plain ODNs. The stability of ODNs was increased with liposomes both in the culture medium and within the cells. Intact liposomal ODNs were detected inside the cells up to 24 hours with gel electrophoresis and phosphor imager analysis. Antisense ODNs had no effect on bcl-2 mRNA levels. Also the proliferation of myeloma cells remained unchanged during the 3-day incubation period. Our study shows that liposomal antisense ODNs targeting bcl-2 of human myeloma cells result in increased stability of ODNs with minimal toxicity. However, further modifications are needed to gain biological effects of antisense ODNs on human myeloma cells.