Referenced in: none

Automatically associated channels: Kv11.1

Title: Differential hERG ion channel activity of ultrasmall gold nanoparticles.

Authors: Annika Leifert, Yu Pan, Anne Kinkeldey, Frank Schiefer, Julia Setzler, Olaf Scheel, Hera Lichtenbeld, Günter Schmid, Wolfgang Wenzel, Willi Jahnen-Dechent, Ulrich Simon

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2013 May 14 , 110, 8004-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23630249

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.