Discriminating nanoparticulate and ionic silver in vivo: Organ-specific distribution and toxicological outcomes via gold-core labeling

The toxicity of metal nanoparticles (MNPs) is closely related to their internal concentration and distribution within organisms. In particular, distinguishing between the distribution of nanoparticles and their released ionic species is critical for understanding their underlying toxicological mechanisms. In this study, we developed a gold-core labeling strategy for Ag NPs, enabling clear discrimination between the biodistribution of nanoparticulate and ionic silver. Our findings revealed that particulate Ag primarily accumulates in the gills and intestine, whereas ionic Ag penetrates into the liver and brain. Within the gills and intestine, Ag NPs were retained in the intestinal mucus but were internalized by gill cells. Given the low glutathione levels in the gill microenvironment, Ag NP exposure significantly induced oxidative stress in gill tissues. In contrast, their impact on the intestine was largely microbiota-related due to limited nanoparticle penetration across the intestinal barrier. Furthermore, natural organic matter substantially reduced Ag NP accumulation in the gills and muscle, thereby providing a protective effect against nanoparticle-induced toxicity in these organs. Overall, this work offers novel insights into the organ-specific distribution and toxicity of MNPs and their dissociated ions, highlighting the crucial roles of both metal speciation and tissue antioxidant capacity in determining toxic outcomes.