Nanoplastics-induced hormesis enhances cadmium bioaccumulation in nematodes by stimulating glutathione synthesis

Nanoplastics (NPs) induce hormesis at environmental concentrations due to their relatively low toxicity; however, this phenomenon can alter the response of biota to coexisting heavy metals, resulting in unknown combined risks. In this study, we investigated the joint effects of cadmium (Cd) and four polystyrene nanoplastics (PS-NPs) with different sizes (100 nm and 500 nm) and surface modifications (-NH₂ and -COOH) on Caenorhabditis elegans, focusing on how NPs-induced bioresponses contribute to Cd accumulation in nematodes. Different from traditional views, the results show that NPs enhance Cd accumulation primarily through hormesis rather than direct adsorption. Coexposure with the four PS-NPs significantly increased Cd bioaccumulation by 1.33-1.71-fold compared to Cd-alone treatments, attributed to elevated storage of glutathione (GSH)-Cd complexes in gut granules. Transcriptomic and metabolomic analyses revealed a 14.0-20.6 % upregulation of metal-response molecules, driven by activation of sulfur-containing amino acid metabolism pathways. These molecular bioresponses doubled GSH synthesis, promoting GSH-Cd complexation and Cd accumulation. Our findings underscore the overlooked role of NPs-induced hormesis in amplifying heavy metal bioaccumulation and associated risks.