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Enhanced percolation and gene expression in tumor hypoxia by PEGylated polyplex micelles.

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.
AuthorsMuri Han, Makoto Oba, Nobuhiro Nishiyama, Mitsunobu R Kano, Shinae Kizaka-Kondoh, Kazunori Kataoka
JournalMolecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 17 Issue 8 Pg. 1404-10 (Aug 2009) ISSN: 1525-0024 [Electronic] United States
PMID19471245 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Micelles
  • Polyethylene Glycols
Topics
  • Animals
  • Cell Hypoxia
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Therapy (methods)
  • Genetic Vectors (chemistry, metabolism)
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Micelles
  • Molecular Structure
  • Polyethylene Glycols (chemistry)
  • Spheroids, Cellular (metabolism)
  • Transfection (methods)

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