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

doi:10.1016/j.jconrel.2009.08.022

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 journal › Article › peer-review

98 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 language	English (US)
Pages (from-to)	77-84
Number of pages	8
Journal	Journal of Controlled Release
Volume	141
Issue number	1
DOIs	https://doi.org/10.1016/j.jconrel.2009.08.022
State	Published - Jan 4 2010
Externally published	Yes

Keywords

Glutathione
Non-viral gene delivery
Pancreatic cancer
Reducible polyplexes
Transfection

ASJC Scopus subject areas

Pharmaceutical Science

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10.1016/j.jconrel.2009.08.022

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title = "Effect of innate glutathione levels on activity of redox-responsive gene delivery vectors",

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.",

keywords = "Glutathione, Non-viral gene delivery, Pancreatic cancer, Reducible polyplexes, Transfection",

author = "Manickam, {Devika S.} and Jing Li and Putt, {David A.} and Zhou, {Qing Hui} and Chao Wu and Lash, {Lawrence H.} and David Oupick{\'y}",

note = "Funding Information: This work was supported by the National Institutes of Health ( 5R01 CA109711 ). We thank Jun Chen for help with synthesis and molecular weight analysis of polycations. ",

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doi = "10.1016/j.jconrel.2009.08.022",

language = "English (US)",

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AU - Manickam, Devika S.

AU - Li, Jing

AU - Putt, David A.

AU - Zhou, Qing Hui

AU - Wu, Chao

AU - Lash, Lawrence H.

AU - Oupický, David

N1 - Funding Information: This work was supported by the National Institutes of Health ( 5R01 CA109711 ). We thank Jun Chen for help with synthesis and molecular weight analysis of polycations.

PY - 2010/1/4

Y1 - 2010/1/4

N2 - 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.

AB - 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.

KW - Glutathione

KW - Non-viral gene delivery

KW - Pancreatic cancer

KW - Reducible polyplexes

KW - Transfection

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

Abstract

Keywords

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