Antiangiogenic gene therapy of experimental pancreatic tumor by sFlt-1 plasmid DNA carried by RGD-modified crosslinked polyplex micelles

Yelena Vachutinsky, Makoto Oba, Kanjiro Miyata, Shigehiro Hiki, Mitsunobu R. Kano, Nobuhiro Nishiyama, Hiroyuki Koyama, Kohei Miyazono, Kazunori Kataoka

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)

Abstract

Disulfide crosslinked polyplex micelles with RGD peptides were formed through ion complexation of thiolated c(RGDfK)-poly(ethylene glycol)-block-poly(l-lysine) (c(RGDfK)-PEG-P(Lys-SH)) and plasmid DNA encoding sFlt-1 and tested for their therapeutic effect in BxPC3 pancreatic adenocarcinoma tumor bearing mice. These micelles, systemically injected, demonstrated significant inhibition of tumor growth up to day 18, as a result of the antiangiogenic effect that was confirmed by vascular density measurements. Significant therapeutic activity of the 15% crosslinked micelle (c(RGDfK)-PEG-P(Lys-SH15)) was achieved by combined effect of increased tumor accumulation, interaction with endothelial cells and enhanced intracellular uptake through receptor-mediated endocytosis. These results suggest that RGD targeted crosslinked polyplex micelles can be effective plasmid DNA carriers for antiangiogenic gene therapy.

Original languageEnglish
Pages (from-to)51-57
Number of pages7
JournalJournal of Controlled Release
Volume149
Issue number1
DOIs
Publication statusPublished - Jan 5 2011
Externally publishedYes

Keywords

  • Antiangiogenic gene therapy
  • Cyclic RGD peptide
  • Poly(ethylene glycol)-block-poly(l-lysine) (PEG-PLys)
  • Polyplex micelle
  • sFlt-1

ASJC Scopus subject areas

  • Pharmaceutical Science

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