Effect of innate glutathione levels on activity of redox-responsive gene delivery vectors

Devika S. Manickam, Jing Li, David A. Putt, Qing Hui Zhou, Chao Wu, Lawrence H. Lash, David Oupický

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

Redox-responsive polyplexes represent a promising class of non-viral gene delivery vectors. The reducible disulfide bonds in the polyplexes undergo intracellular reduction owing to the presence of high concentrations of reduced glutathione (GSH). Available evidence suggests improved transfection activity of redox-sensitive polyplexes upon artificial modulation of intracellular GSH. This study investigates the effect of innate differences in GSH concentration in a panel of human pancreatic cancer cell lines on activity of reducible polyplexes of the four major classes of nucleic acid therapeutics: plasmid DNA (pDNA), messenger RNA (mRNA), antisense oligodeoxynucleotides (AON) and siRNA. In general, reducible polyplexes of linear poly(amido amines) (PAA) show improved activity compared to non-reducible polyplexes of PAA. Results demonstrate that increased GSH levels are associated with improved transfection of mRNA polyplexes but no clear trend is observed for pDNA, AON and siRNA polyplexes.

Original languageEnglish (US)
Pages (from-to)77-84
Number of pages8
JournalJournal of Controlled Release
Volume141
Issue number1
DOIs
StatePublished - Jan 4 2010

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Keywords

  • Glutathione
  • Non-viral gene delivery
  • Pancreatic cancer
  • Reducible polyplexes
  • Transfection

ASJC Scopus subject areas

  • Pharmaceutical Science

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