Sulfidation Affects Macrophage Uptake of Metal-Based Nanomaterials by Dictating Protein Corona Compositions and Aggregation States Collectively

Metal-based
nanomaterials are one of the most widely used classes
of nanomaterials. Understanding their human exposure is critical for
the risk management of these nanomaterials. Once released into the
environment, metal nanomaterials are prone to undergo sulfidation.
This process significantly alters the physicochemical properties of
the nanomaterials and subsequently, dictates the extents and pathways
of exposure. Here, we show that sulfidation of nanosized Ag, ZnO,
CuO, and Cu2O affects their macrophage uptake to varied
degrees, by differentially regulating protein corona compositions
and aggregation states of the nanomaterials. Sulfidation-induced changes
in hydrodynamic diameters determine whether macrophage uptake occurs
through endocytosis or phagocytosis. For a given uptake pathway, the
extents of uptake depend on macrophage recognition of protein corona,
the compositions of which are largely influenced by sulfidation. Specifically,
increased abundance of transferrin and low-density apolipoprotein
C2 in the corona as affected by sulfidation promotes clathrin-mediated
endocytosis, while the enrichment of complement factor H facilitates
uptake by complement receptor-mediated phagocytosis. The findings
advance our understanding on the nanospecific mechanisms governing
environmental behaviors and implications of nanomaterials, and further
underline the importance of taking into account the aging processes
in the risk management of these materials.