Comparative transfection studies of human ovarian carcinoma cells in vitro, ex vivo and in vivo with poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes

Background Poly(2-(dimethylamino) ethyl methacrylate) (p(DMAEMA)) can be us ed successfully for in vitro transfection of different cell lines, includin g the OVCAR-3 human ovarian carcinoma cell line. The aim of this study was to investigate whether it is possible to transfect OVCAR-3 cells in vivo wi th polyplexes containing p(DMAEMA). Methods In order to understand the generally observed gap between in vitro and in vivo transfection, we gradually went from in vitro to in vivo transf ection of OVCAR-3 cells, while keeping the exposure conditions the same, as far as possible. To find the reason for the negligible degree of in viva t ransfection, in vitro cultured OVCAR-3 cells were transfected in the presen ce of peritoneal ascites fluid. Next, the influence of hyaluronic acid, one of the ascites components, on the transfection efficiency was studied. Results P(DMAEMA)-containing polyplexes can transfect OVCAR-3 cells in vitr o with an overall transfection efficiency of 10%. Cells grown in vivo can b e transfected ex vivo with p(DMAEMA)/plasmid complexes with an overall tran sfection efficiency of similar to 1-2%. When transfection complexes are inj ected ip. into nude mice bearing OVCAR-3 cells in the peritoneal cavity, th e degree of in vivo transfection efficiency achieved is negligible. In vitro cultured OVCAR-3 cells were also transfected with polyplexes in th e presence of peritoneal ascites fluid. The results indicate that one or mo re components of ascites had a negative effect on the transfection efficien cy of p(DMAEMA)-containing polyplexes. To elucidate which component(s) of a scites may have interfered, the influence of hyaluronic acid, one of the as cites components, on the transfection efficiency was studied. The outcome s uggests that hyaluronic acid may have induced a negative effect on the tran sfection capability of p(DMAEMA)-containing polyplexes. Conclusion P(DMAEMA) is an efficient transfectant in vitro and ex vivo. How ever, transfected cells were not detected in vivo which may be caused by a negative influence of components of the ascites fluid. Copyright (C) 1999 J ohn Wiley & Sons, Ltd.