Enhancement of liposomal gene delivery in human breast cancer cells by dimethyl sulfoxide.
Non-toxic concentrations ( 1%) of dimethyl sulfoxide (DMSO) enhance the liposomal delivery of DNA to both MCF-7 and MDA-MB-231 human breast tumor cells. Uptake of SV-40-luciferase was enhanced in MCF-7 cells by 14-fold while uptake of CMV-beta-galactosidase was increased 10-fold. In MDA-MB-231 cells, uptake of SV-40-luciferase was increased by approximately 70%. A mixture of ethanol and polyethylene glycol (45:55) at a concentration of 1% produced less pronounced improvements in transgene delivery to MCF-7 cells (a 70% increase in SV-40-luciferase uptake and a 4-fold increase in CMV-beta-galactosidase uptake) but no improvement in SV-40-luciferase gene delivery to MDA-MB-231 cells. These studies suggest that select pharmaceutical adjuvants which dissolve clinically useful drugs may have promise as non-toxic vehicles for improving transgene delivery. However, the relative effectiveness of these adjuvants is likely to vary depending on both the nature of the gene being delivered as well as the tumor cell which is the target for uptake of the exogenous gene.
Jain
P T
PT
Departments of Pharmacology, Toxicology and Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
Gewirtz
D A
DA
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D018014:Gene Transfer Techniques; D006801:Humans; D008081:Liposomes; D011092:Polyethylene Glycols / Q000494:pharmacology; D012997:Solvents / Q000494:pharmacology*; D014162:Transfection / Q000187:drug effects; D014407:Tumor Cells, Cultured
D008081:Liposomes; D012997:Solvents; D000431:Ethanol; D011092:Polyethylene Glycols; D004121:Dimethyl Sulfoxide