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Differential hERG ion channel activity of ultrasmall gold nanoparticles
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Understanding the mechanism of toxicity of nanomaterials remains a challenge with respect to both mechanisms involved and product regulation. Here we show toxicity of ultrasmall gold nanoparticles (AuNPs). Depending on the ligand chemistry, 1.4-nm-diameter AuNPs failed electrophysiology-based safety testing using human embryonic kidney cell line 293 cells expressing human ether-á-go-go-Related gene (hERG), a Food and Drug Administration-established drug safety test. In patch-clamp experiments, phosphine-stabilized AuNPs irreversibly blocked hERG channels, whereas thiol-stabilized AuNPs of similar size had no effect in vitro, and neither particle blocked the channel in vivo. We conclude that safety regulations may need to be reevaluated and adapted to reflect the fact that the binding modality of surface functional groups becomes a relevant parameter for the design of nanoscale bioactive compounds.
In this study, the toxicity of ultrasmall gold nanoparticles (AuNPs) are investigated using 1.4-nm-diameter phosphine- and thiol-stabilized AuNPs in a electrophysiology-based safety test using human embryonic kidney cell line 293 cells expressing human ether-á-go-go-Related gene (hERG), which is a Food and Drug Administration-established drug safety test.
Peer Reviewed Journal Article
Exposure Or Hazard Target
Method Of Study
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Proceedings of the National Academy of Sciences, 110(20): 8004-8009 (May 2013)
Proceedings of the National Academy of Sciences of the United States of America
Leifert A, Pan Y, Kinkeldey A, Schiefer F, Setzler J, Scheel O, Lichtenbeld H, Schmid G, Wenzel W, Jahnen-Dechent W, Simon U
Last updated on June 5, 2013
This work is supported in part by the Nanoscale Science and Engineering Initiative of the National Science Foundation
under NSF Award Number EEC-0118007.
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