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

Muri Han, Makoto Oba, Nobuhiro Nishiyama, Mitsunobu R. Kano, Shinae Kizaka-Kondoh, Kazunori Kataoka

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1404-1410
Number of pages7
JournalMolecular Therapy
Volume17
Issue number8
DOIs
Publication statusPublished - 2009
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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