Journal
ENVIRONMENTAL SCIENCE-NANO
Volume 7, Issue 5, Pages 1373-1387Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c9en01348b
Keywords
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Funding
- French Infrastructure for Integrated Structural Biology (FRISBI) [ANR-10-INSB-05-02]
- GRAL, a project of the University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBHEUR-GS [ANR-17-EURE-0003]
- Auvergne Rhone-Alpes Region
- Fondation Recherche Medicale (FRM)
- fonds FEDER
- GIS-Infrastructures en Biologie Sante et Agronomie (IBISA)
- French Government's Investissements d'Avenir ANR program, through the A*MIDEX project [ANR-11-LABX-0064, ANR-11-IDEX-0001-02]
- CBH-EUR-GS [ANR-17EURE-0003]
- CEA Transversal Programs Toxicology and Nanoscience through the NanoTox-RX grant
- CEA DRF-Impulsion grant FIB-Bio
- Universite Grenoble Alpes-AGIR grant NanoSilverSafe and IRS NanoBIS grant
- RHU program [ANR-16-RHUS-0005]
- CMIRA Accueil Sup 2016 fellowship
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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.
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