In regard to gene vectors for cancer gene
therapy, their percolation into the
tumor tissue should be essential for successful outcome. Here, we studied the
tumor penetrability of nonviral vectors (polyplexes) after incubation with the multicellular
tumor spheroid (MCTS) models and intratumoral (i.t.) injection into subcutaneous
tumors. As a result,
polyethylene glycolated (PEGylated), core-shell type polyplexes (polyplex
micelles) showed facilitated percolation and improved transfection inside the
tumor tissue, whereas conventional polyplexes from cationic
polymers exhibited limited percolation and localized transfection. Furthermore, the transfection of
hypoxia-responsive plasmid demonstrated that polyplex
micelles allowed the transfection to the hypoxic region of the
tumor tissue in both in vitro and in vivo experiments. To the best of our knowledge, our results demonstrated for the first time that polyplex
micelles might show improved
tumor penetrability over cationic polyplexes, thereby achieving transfection into the inside of the
tumor tissue.