Polystyrene nanoplastics amplify arsenite-induced toxicity to human serum albumin: Potentiated inhibition via complexation.

Arsenite (As(III)) classified as Group 1 carcinogen, frequently cooccurs with polystyrene nanoplastics (PS-NPs) in environmental matrices. As emerging pollutants of global concern, PS-NPs can serve as carriers for As(III) and amplify human exposure risks through biomagnification in the food chain. While PS-NPs are known to enhance the toxicity of environmental pollutants toward functional proteins, the underlying mechanisms remain unclear. Particularly, the combined toxic effects of As(III) and PS-NPs on circulatory carrier protein-human serum albumin (HSA) remain poorly elucidated. The present work focuses on the mechanistic interactions between As(III)-adsorbed PS-NPs and HSA. Results indicate that PS-NPs reversed the biological effect of As(III) on HSA. While As(III) alone (50 mg/L) activated HSA esterase activity (113.75 %), PS-NPs@As(III) at equivalent concentrations caused significant inhibition (60 %), exceeding that of PS-NPs alone (86.88 %, 10 mg/L). As(III) binds near HSA Sudlow site I (IIA). The binding of As(III) to HSA is primarily enthalpy-driven, involving hydrogen bonds and van der Waals forces, disrupting the solvation shell on HSA and inducing smaller new complexes. Conversely, PS-NPs and PS-NPs@As(III) utilized entropy-driven hydrophobic interactions, forming "protein corona". Crucially, As(III) adsorption onto PS-NPs enhanced both binding affinity to HSA and protein corona formation. Transmission electron microscopy provided direct morphological evidence of a significantly thicker protein corona layer in the PS-NPs@As(III)-HSA system. HSA backbone expansion, secondary structure disruption and fluorescence sensitization provide the structural basis for potent inhibition of PS-NPs@As(III). Our findings offer mechanistic insights to support future toxicological investigations of nanoplastics and their co‑pollutants with human circulatory proteins at environmentally relevant concentrations.