Enhanced Percolation and Gene Expression in Tumor Hypoxia by PEGylated Polyplex Micelles |
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| Authors: | Muri Han Makoto Oba Nobuhiro Nishiyama Mitsunobu R Kano Shinae Kizaka-Kondoh Kazunori Kataoka |
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| Affiliation: | 1. Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan;2. Department of Clinical Vascular Regeneration, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;3. Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;4. Center for NanoBio Integration, The University of Tokyo, Tokyo, Japan;5. Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;6. Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Graduate School of Medicine, Kyoto, Japan;7. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi, Japan |
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| Abstract: | 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. |
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