Mild Sulfidation Aggravates the Dissolution and Cytotoxicity of Silver Nanoparticles in Mammalian Cells

Silver nanoparticles (Ag NPs) have been extensively utilized in food preservation, disinfection, personal care, and medical applications. Upon exposure to biological environments, pristine Ag NPs are susceptible to transformation into other chemical forms through processes, such as sulfidation. Although the majority of published literature indicates that sulfidation can significantly mitigate the toxicity of Ag NPs, it remains unknown how the degree of sulfidation influences nano-bio interactions of Ag NPs in mammalian cells. To elucidate the potential role of sulfidation in the cytotoxicity of Ag NPs, we first synthesized and characterized Ag NPs with varying degrees of sulfidation. Unexpectedly, while high-degree sulfidation resulted in a reduction of the cytotoxicity of Ag NPs, mild sulfidation intensified their toxicity. Further mechanistic investigations revealed that the oxidative dissolution of low-degree sulfidized Ag NPs enhanced the release of Ag⁺, promoted the generation of reactive oxygen radicals, and aggravated lipid peroxidation within cells, thereby activating ferroptosis through inhibiting the expression of ferritin and glutathione peroxidase 4.