Nanoplastics amplify 6PPD ocular toxicity in zebrafish

Nanoplastics and tire-derived chemicals are ubiquitous co-pollutants in aquatic environments, originating from road runoff and posing potential risks to vertebrate development through enhanced bioavailability and synergistic toxicity. Polystyrene nanoplastics (PS) can adsorb hydrophobic organics like the antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), acting as vectors that increase tissue accumulation and exacerbate oxidative stress, while 6PPD alone disrupts mitochondrial function and induces sublethal effects in exposed organisms. The vertebrate eye, with its direct environmental exposure and sensitive neural structures, is particularly vulnerable, yet the combined impact of PS and 6PPD on visual morphogenesis remains underexplored. Here we show that co-exposure to environmentally relevant concentrations of PS (1 mg L⁻¹) and 6PPD (0.1–0.8 mg L⁻¹) markedly potentiates ocular toxicity compared to individual exposures, manifesting as myopia-like malformations, increased cell death, and impaired phototaxis. We integrated phenotypic, histological, and multi-omics analyses using zebrafish embryos as a model. Our results show PS-enhanced bioaccumulation of 6PPD in ocular tissues, leading to severe lens and retinal damage, aberrant vascularization, disrupted myelination, and dysregulated pathways including serine proteolysis, retinoic acid metabolism, and ferroptosis-linked oxidative stress. These findings demonstrate nanoplastic-chemical interactions as an emerging threat to aquatic visual function, with implications for survival behaviors and broader ecosystem health under pervasive pollution.