In vivo delivery to tumors of DNA complexed with linear polyethylenimine

Synthetic gene delivery vectors have shown promise in several organs, inclu ding brain and lung. Tumor cell targeting, however, is still hindered by th eir law efficacy, A linear polyethylenimine (L-PEI, Exgen 500) was found to be effective in vivo. Our first attempts to use L-PEI for intratumoral gen e delivery were not successful, presumably because of poor diffusion of the complexes within the tumor mass after injection with a syringe. Here we sh ow that L-PEI-mediated transfection can be strongly enhanced when the compl exes are delivered slowly into a solid tumor mass, using a micropump, Furth ermore, L-PEI/DNA complexes actively transfect pseudocystic tumor cells whe n injected into the cyst cavity. In both cases L-PEI induced a significant and long-lasting (greater than or equal to 15 days) expression of the repor ter gene. Finally, even though systemic delivery of L-PEI/DNA complexes lea ds to high levels of expression in the lung, this method is not adapted for transfection of subcutaneous tumors implanted in the thigh nor for transfe ction of lung metastases. Altogether, these results show that L-PEI has pro mising features for transfection of tumor cells, provided that the mode of delivery is adapted.