Modified microplex vector enhances transfection of cells in culture while maintaining tumour-selective gene delivery in-vivo.
A non-commercial liposome (dimethyl dioctadecyl ammonium bromide:dioleoyl phosphatidylethanolamine) was compared with a commercial variety (Lipofectamine) for transfection of cultured rat adenocarcinoma cells and in an in-vivo kidney tumour model. Transfection of the cells in culture and in tumours in-vivo was variable with both types of liposomes. A high-dose microplex (lipoplex-microsphere) vector enhanced liposome-mediated transfection of cells in culture. When these high-dose microplexes were tested in-vivo, they were better than both microspherical and liposomal delivery modes in terms of transgene expression levels and the tumour-to-normal tissue ratio of gene delivery. Microplexes have been demonstrated to be capable of not only selective delivery of plasmids to solid tumours, but also of increasing transfection in cell culture, a finding that may be used in ex-vivo transfection studies. It is hypothesized that microspheres anchored the combination vector closer to the cultured cells, allowing attached liposomes to gain easier access into cells. In-vivo, microspheres permitted the microplexes to selectively deliver their genetic payload within the tumour tissue, from where the action of cationic liposomes on cellular membranes facilitated increased access of plasmids into the cytosol of target cells.
Dass
Crispin R
CR
Charles Sturt University, Box 588, Wagga Wagga, NSW 2678, Australia. cdass@medau.jnj.com
Burton
Mark A
MA
D002411:Cation Exchange Resins / Q000737:chemistry*; D002412:Cations; D002462:Cell Membrane; D004337:Drug Carriers / Q000737:chemistry*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry*; D007680:Kidney Neoplasms / Q000473:pathology; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008863:Microspheres; D010957:Plasmids; D014162:Transfection; D014407:Tumor Cells, Cultured
D002411:Cation Exchange Resins; D002412:Cations; D004337:Drug Carriers; D007202:Indicators and Reagents; D008055:Lipids; C086724:Lipofectamine; D008081:Liposomes