Differential hERG ion channel activity of ultrasmall gold nanoparticles
Differential hERG ion channel activity of ultrasmall gold nanoparticles
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DOI：
10.1073/pnas.1220143110
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发表时间：
2013-05-14
影响因子：
11.1
通讯作者：
Simon, Ulrich
中科院分区：
文献类型：
--
作者：
Leifert, Annika;Pan, Yu;Simon, Ulrich
了解纳米材料的毒性机制在所涉及的机制和产品监管方面仍然是一个挑战。在这里，我们展示了超小金纳米颗粒(AuNPs)的毒性。根据配基化学的不同，直径1.4 nm的AuNPs未能通过使用表达人类乙醚-a-GO-GO相关基因(HERG)的人胚胎肾细胞系293细胞进行的基于电生理学的安全性测试，这是美国食品和药物管理局(FDA)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，而尺寸相似的硫醇稳定的AuNPs在体外没有作用，两种颗粒都不能在体内阻断该通道。我们的结论是，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相关参数。
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-a-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.