The impact on human health of long-term exposure to low doses of silver nanoparticles (AgNPs) remains understudied. Cellular studies have shown the intracellular dissolution of AgNPs within endolysosomes followed by Ag(I) binding to biomolecular thiolate-containing molecules. However, the precise subcellular distribution of Ag(I) and the nature of the disrupted physiological pathways remained unknown. Novel imaging approaches enabled us to visualize the trafficking of AgNP-containing lysosomes towards a perinuclear location and a nuclear transfer of Ag(I) species with accumulation in the nucleoli. These Ag(I) species impaired nuclear receptor activity, disrupting critical mechanisms of liver physiology in low dose exposure scenarios, thus justifying further research into defining a framework for the safe use of AgNPs.

中文翻译：

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暴露于银纳米颗粒时银离子的核易位和肝细胞核受体损伤

长期暴露于低剂量的银纳米颗粒（AgNPs）对人体健康的影响尚待研究。细胞研究表明，AgNP在胞内溶酶体内溶解于细胞内，然后Ag（I）与含生物分子硫醇盐的分子结合。然而，Ag（I）的确切亚细胞分布和破坏的生理途径的性质仍然未知。新颖的成像方法使我们能够可视化包含AgNP的溶酶体向核周位置的运输以及Ag（I）物种在核仁中的积累的核转移。这些银（我物种损害了核受体的活性，在低剂量暴露的情况下破坏了肝脏生理的关键机制，因此有理由进行进一步的研究来确定安全使用AgNP的框架。