Strathprints logo
Strathprints Home | Open Access | Browse | Search | User area | Copyright | Help | Library Home | SUPrimo

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

Meidan, V.M. and Glezer, J. and Salomon, S. and Sidi, Y. and Barenholz, Y. and Cohen, J.S. and Lilling, G. (2006) Specific lipoplex-mediated antisense against Bcl-2 in breast cancer cells: a comparison between different formulations. Journal of Liposome Research, 16 (1). pp. 27-43. ISSN 0898-2104

Full text not available in this repository. (Request a copy from the Strathclyde author)

Abstract

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 cationic 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.

Item type: Article
ID code: 7587
Keywords: G3139, antisense oligonucleotide, DOTAP, ceramide carbamoyl spermine, pharmacology, Pharmacy and materia medica, Pharmacology
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Strathprints Administrator
    Date Deposited: 07 Apr 2009 12:39
    Last modified: 04 Sep 2014 17:12
    URI: http://strathprints.strath.ac.uk/id/eprint/7587

    Actions (login required)

    View Item