Silver Nanoparticles Induce Apoptosis in HepG2 Cells through Particle-Specific Effects on Mitochondria

Silver nanoparticles (AgNPs) have been widely used in biomedical and consumer products. It remains challenging to distinguish the toxicity of AgNPs derived from the particle form or the released silver ions (Ag⁺). In this study, the toxic effects of two citrate-coated AgNPs (20 and 100 nm) and Ag⁺ were investigated in hepatoblastoma cells (HepG2 cells). The suppression tests showed that AgNPs and Ag⁺ induced cell apoptosis via different pathways, which led us to speculate on the AgNP-induced mitochondrial damage. Then, the mitochondrial damages induced by AgNPs and Ag⁺ were compared under the same intracellular Ag⁺ concentration, showing that the mitochondrial damage might be mainly attributed to Ag nanoparticles but not to Ag⁺. The interaction between AgNPs and mitochondria was analyzed using a scattered light imaging method combined with light intensity profiles and transmission electron microscopy. The colocalization of AgNPs and mitochondria was observed in both NP20- and NP100-treated HepG2 cells, indicating a potential direct interaction between AgNPs and mitochondria. These results together showed that AgNPs induced apoptosis in HepG2 cells through the particle-specific effects on mitochondria.