Cellular uptake, intracellular trafficking and cytotoxicity of silver nanoparticles

Silver nanoparticles (Ag NPs) are used in consumer products and wound dressings due to their antimicrobial properties. However, in addition to toxic effects on microbes, Ag NPs can also induce stress responses as well as cytotoxicity in mammalian cells. We observed that Ag NPs are efficiently internalized via scavenger receptor-mediated phagocytosis in murine macrophages. Confocal and electron microscopy analysis revealed that internalized Ag NPs localize in the cytoplasm. Ag NPs cause mitochondrial damage, induce apoptosis and cell death. These effects were abrogated in presence of Ag ion-reactive, thiol-containing compounds suggesting the central of Ag ions in Ag NP toxicity. Quantitative image analysis revealed that intracellular dissolution of Ag NPs occurs about 50 times faster than in water. In conclusion, we demonstrate for the first time that Ag NPs are internalized by scavenger receptors, trafficked to cytoplasm and induce toxicity by releasing Ag ions.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Macrophages are the most sensitive cell line to silver nanoparticle-induced cytotoxicity. ► Silver nanoparticles are internalized via scavenger receptors and trafficked to cytosol. ► Mitochondrial damaging potential of silver nanoparticles is mediated by silver ions. ► Cytotoxicity of silver nanoparticles is due to silver ions. ► Intracellular presence of silver ions is demonstrated for the first time.