title: Differential hERG ion channel activity of ultrasmall gold nanoparticles.
abstract: 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.
authors: Institute of Inorganic Chemistry and Jülich Aachen Research Alliance-Fundamentals of Information Technology, Biointerface Laboratory, Rheinisch-Westfälische Technische Hochschule Aachen University, 52074 Aachen, Germany.
authors: Annika
authors: A
authors: Leifert
authors: Yu
authors: Y
authors: Pan
authors: Anne
authors: A
authors: Kinkeldey
authors: Frank
authors: F
authors: Schiefer
authors: Julia
authors: J
authors: Setzler
authors: Olaf
authors: O
authors: Scheel
authors: Hera
authors: H
authors: Lichtenbeld
authors: Günter
authors: G
authors: Schmid
authors: Wolfgang
authors: W
authors: Wenzel
authors: Willi
authors: W
authors: Jahnen-Dechent
authors: Ulrich
authors: U
authors: Simon
mesh_terms: D000818:Animals; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography / Q000379:methods; D004594:Electrophysiology / Q000379:methods; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism / Q000502:physiology*; D006046:Gold / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D036103:Nanotechnology / Q000379:methods; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000737:chemistry; D011485:Protein Binding; D013696:Temperature
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D026902:Potassium Channel Blockers; D006046:Gold
keywords: complementarity; gold cluster; nanotoxicology; shape
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