H. Ollikainen et al., LIPOSOMAL TARGETING OF BCL-2 ANTISENSE OLIGONUCLEOTIDES WITH ENHANCEDSTABILITY INTO HUMAN MYELOMA CELL-LINES, Leukemia & lymphoma, 24(1-2), 1996, pp. 165-174
Cationic liposomes improve the delivery of antisense oligonucleotides
(ODNs) into cells. However, there is marked variability in the cellula
r uptake of ODNs into different cell lines. We used liposomes containi
ng dimethyloctadecylammonium bromide (DDAB) and dioleoylphosphatidylet
hanolamine (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 l
iposomes both in the culture medium and within the cells. Intact lipos
omal ODNs were detected inside the cells up to 24 hours with gel elect
rophoresis 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 li
posomal antisense ODNs targeting bcl-2 of human myeloma cells result i
n increased stability of ODNs with minimal toxicity. However, further
modifications are needed to gain biological effects of antisense ODNs
on human myeloma cells.