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Opposing influence of intracellular and membrane thiols on the toxicity of reducible polycations
Wu, C; Li, J; Zhu, Y; Chen, J; Oupicky, D
2013
发表期刊BIOMATERIALS
卷号34期号:34页码:8843-8850
摘要Toxicity of polycations has been recognized since their first use in gene delivery. Bioreducible polycations attract attention because of their improved safety due to selective intracellular degradation by glutathione (GSH). Here we present a systematic study of the toxicity of bioreducible poly(amido amine)s (PAA). PAA with increasing content of disulfide bonds were synthesized by Michael addition. Toxicity of PAA was evaluated in two cell lines with different innate levels of intracellular GSH. Increasing the content of disulfide bonds decreased the toxicity of PAA, with more significant decrease observed in cells with high GSH. Depleting intracellular GSH by diethyl maleate resulted in increased toxicity of bioreducible PAA. In contrast, increasing the GSH concentrations by growing cells in hypoxic conditions resulted in further decreased toxicity compared with cells grown in normoxic conditions. The presence of exofacial plasma membrane thiols selectively increased toxicity of bioreducible PAA while having no effect on non-degradable controls. These results improve our understanding of the cellular mechanisms of polycation toxicity. They also shed light on the opposing effects of different cellular thiol pools on the toxicity of bioreducible polycations. (C) 2013 Elsevier Ltd. All rights reserved.
关键词Non-viral gene delivery Polycations Bioreducible polycations Glutathione Toxicity
学科领域Engineering; Materials Science
DOI10.1016/j.biomaterials.2013.07.095
收录类别SCI
WOS记录号WOS:000324450600028
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ihep.ac.cn/handle/311005/224313
专题多学科研究中心
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GB/T 7714
Wu, C,Li, J,Zhu, Y,et al. Opposing influence of intracellular and membrane thiols on the toxicity of reducible polycations[J]. BIOMATERIALS,2013,34(34):8843-8850.
APA Wu, C,Li, J,Zhu, Y,Chen, J,&Oupicky, D.(2013).Opposing influence of intracellular and membrane thiols on the toxicity of reducible polycations.BIOMATERIALS,34(34),8843-8850.
MLA Wu, C,et al."Opposing influence of intracellular and membrane thiols on the toxicity of reducible polycations".BIOMATERIALS 34.34(2013):8843-8850.
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