Widespread use of metal oxide nanoparticles (nMOXs), specifically nCuO and nZnO, drive their accumulation and biological impacts in aquatic ecosystem. Their co-occurrence with microplastics complicates nMOXs fate and interaction dynamics via heteroaggregation and dissolution, potentially amplifying cellular toxicity. Although humic acid (HA) modulates their bioavailability via eco-corona formation, its protective efficacy remains highly nanoparticle-dependent, presenting a critical knowledge gap. Thus, this study assessed how HA (10 mg L^–1) modulates the individual and combined effects of polystyrene microplastics (mPS, 1 mg L^–1) and two nMOXs (nCuO and nZnO, 1 mg L^–1) on microalga Chlorella vulgaris following a 96-h exposure. Compare to individual exposure, combined mPS–nMOX exposure elicited severe oxidative stress, membrane disintegration, mitochondrial dysfunction and nutrient depletion via heteroaggregation-driven cellular internalisation. While mPS–nZnO induced greater algal toxicity than mPS–nCuO due to higher ion release, HA mitigated this toxicity by forming protective eco-coronas that enhanced colloidal stability and curtailed cell–pollutant interactions, suppressing mPS–nCuO more effectively than mPS–nZnO via stronger complexation. These findings revealed that the protective efficacy of HA against mPS–nMOX toxicity depends on nanoparticle types, with HA conferring greater mitigation of mPS–nCuO than mPS–nZnO toxicity through preferential Cu²⁺ complexation that restricts bioavailable ion fractions. Mechanistically, HA-driven eco-coronas govern nanoparticle–microplastic interactions, offering novel insights to refine ecological risk frameworks and guide safe-by-design strategies for managing aquatic co-contamination.

Keywords: metal oxide nanoparticles; microplastic pollution; natural organic matter; environmental risk; freshwater algae; physiological response