Institute of Inorganic Chemistry and Jülich Aachen Research Alliance-Fundamentals of Information Technology, Biointerface Laboratory, Rheinisch-Westfälische Technische Hochschule Aachen University, 52074 Aachen, Germany.
Proc Natl Acad Sci U S A. 2013 May 14;110(20):8004-9. doi: 10.1073/pnas.1220143110. Epub 2013 Apr 29.
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.
理解纳米材料毒性的机制仍然是一个挑战，无论是涉及的机制还是产品监管。在这里，我们展示了超小的金纳米粒子（AuNPs）的毒性。根据配体化学，1.4nm 直径的 AuNPs 在基于电生理学的安全性测试中未能通过表达人类 ether-á-go-go-Related 基因（hERG）的人胚肾细胞系 293 细胞，这是美国食品和药物管理局建立的药物安全性测试。在膜片钳实验中，膦稳定的 AuNPs 不可逆地阻断 hERG 通道，而具有相似大小的硫醇稳定的 AuNPs 在体外没有影响，并且两种粒子都没有在体内阻断通道。我们得出结论，安全法规可能需要重新评估和调整，以反映这样一个事实，即表面官能团的结合方式成为设计纳米级生物活性化合物的一个相关参数。
