Cadmium (Cd) and micro/nanoplastics frequently coexist in aquatic environments, yet how plastic particles modulate heavy metal toxicity in microalgae remains poorly understood. Here, the freshwater microalga Chlamydomonas reinhardtii was employed to investigate the interaction between polystyrene nanoplastics (PS-NPs) and Cd at physiological, biochemical, ultrastructural, and molecular levels. Among the tested particle sizes, 500 nm PS-NPs exhibited the strongest observed growth inhibition under Cd co-exposure and were therefore selected for subsequent mechanistic investigation. Cd-NPs co-exposure caused pronounced growth inhibition, pigment disturbance, oxidative damage, and chloroplast ultrastructural disruption. Notably, EDTA-resistant cellular Cd accumulation was lower under simultaneous Cd-NPs co-exposure than under Cd exposure alone, indicating that the greater biological impairment observed under co-exposure was not attributable to an increased EDTA-resistant cellular Cd burden. Integrated transcriptomic and metabolomic analyses revealed coordinated disturbances in metal/redox homeostasis, membrane lipid remodeling, pigment metabolism, nitrogen redistribution, and central carbon metabolism. These findings support a model in which NPs modify Cd-associated biological responses without increasing EDTA-resistant cellular Cd retention. This study provides new insights into how nanoplastics may modify metal toxicity outcomes in freshwater microalgae and highlights the potential importance of incorporating organism-level stress responsiveness into ecological risk assessment of emerging aquatic contaminants.
