Sulfidation of Ag and ZnO Nanomaterials Significantly Affects Protein Corona Composition: Implications for Human Exposure to Environmentally Aged Nanomaterials

The physicochemical properties of engineered nanomaterials can change drastically during aging in the environment. Understanding how these changes influence protein corona formation on nanomaterials is critical for accurately predicting the human exposure risks of aged nanomaterials. Here, we show that sulfidation, a prevalently occurring environmental aging process, of Ag and ZnO nanomaterials significantly affected the protein compositions of the hard corona formed in human saliva, sweat, and bronchoalveolar lavage fluid, corresponding to three most common exposure pathways, that is, ingestion, dermal contact, and inhalation. In particular, a diverse variety of proteins selectively associated with either sulfidized or pristine nanomaterials. Random forest classification of the proteomic data revealed that this selective protein adsorption process was mainly dictated by electrostatic interaction, hydrophobic interaction, and steric hindrance between proteins and nanomaterials, which were susceptible to the changes in surface charge, hydrophobicity, and aggregation status of nanomaterials induced by sulfidation. Furthermore, even for the proteins that do not exhibit distinct adsorption selectivity between sulfidized and pristine nanomaterials, sulfidation altered the extents of impact of nanomaterials on the conformation and likely functions of the adsorbed proteins. These findings unearth a previously neglected mechanism via which environmental sulfidation process mediates the biological effects of soft-metal-containing nanomaterials.