Specific lipoplex-mediated antisense against Bcl-2 in breast cancer cells: A comparison between different formulations

Victor M. Meidan*, Judith Glezer, Sharona Salomon, Yechezkel Sidi, Yechezkel Barenholz, Jack S. Cohen, Gila Lilling

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


G3139 is an antisense oligonucleotide (ODN) that can down-regulate bcl-2, thus potentially acting as a potent anticancer drug. However, effective therapy requires efficient ODN delivery, which may be achieved by employing G3139 lipoplexes. Yet, lipofection is a complex, multifactorial process that is still poorly understood. In order to shed more light on this issue, we prepared 18 different G3139 lipoplex formulations and compared them in terms of their capability to transfect MCF-7 breast cancer cells. Each formulation was composed of a canonic lipid and sometimes a helper lipid. The cationic lipid was either DOTAP (N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride), DC-CHOL (3β[N-(N′,N′-dimethylaminoethane)carbamoyl]-cholesterol), or CCS (ceramide carbomoyl spermine). The helper lipid was either DOPC, DOPE, or cholesterol. Each lipid combination existed in two different structural forms - either large unilamellar vesicles (∼100 nm LUV) or unsized heterolamellar vesicles (UHV). Cell proliferation assays were used to evaluate the cytotoxicity of G3139 lipoplexes, control cationic lipid assemblies, and free G3139. Western blots were used to confirm the specific activity of G3139 as an anti-bcl-2 antisense agent. We determined that treatment of MCF-7 cells with G3139:CCS lipoplexes (UHV-derived) produced a maximal 50-fold improvement in antisense efficacy compared to treatment with free G3139. The other G3139 lipoplexes were not superior to free G3139. Thus, successful lipofection requires precise optimization of lipoplex lipid composition, structure, and concentration.

Original languageEnglish
Pages (from-to)27-43
Number of pages17
JournalJournal of Liposome Research
Issue number1
StatePublished - Feb 2006
Externally publishedYes


FundersFunder number
Iowa Science Foundation30/98-16.1, 62/03
Ministry of Health, State of Israel


    • Antisense oligonucleotide
    • Ceramide carbamoyl spermine (CCS)
    • DC-Chol
    • DOTAP
    • G3139


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