There is a severe lack of understanding of the effects of micro/nanoplastics on human proteins and cells, especially in the presence of organic pollutants. Herein, both in vivo and in vitro assays are conducted to structurally evaluate blood protein complexed with perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) as well as their coronas formed on polystyrene nanoplastics (PNs). PFOS is bound to serum albumin (SA) about 4 times as firmly as PFOA, which is not influenced by protein corona formation onto PN surfaces. However, the small molecular binding dramatically suppresses SA–PN aggregation. Low pH weakens the protein interaction of PFOS while not PFOA, which is also independent of PN adsorption, but the interaction with SA is still stronger for PFOS than PFOA, indicating higher serum persistence and risks. The presence of PN suppresses the cellular uptake of the chemicals and attenuates cytotoxicity due to low bioavailability. Overall, these results provide fundamental information on the ternary interaction mode of protein, particle, and organic pollutants in physiological environments with varying pH, as well as the subsequent cellular responses.
