Nuclear translocation of silver ions and hepatocyte nuclear receptor impairment upon exposure to silver nanoparticles

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.