Co-Exposure to ZnO nanoparticles and imidacloprid enhances phytotoxicity in lettuce via accumulation-driven metabolic disruption

The continuous accumulation of metallic nanoparticles and pesticide residues in agroecosystems poses potential risks to food safety and plant health, yet their potential interactive toxicity remains poorly understood. Here, we investigated the mutual effects of zinc oxide nanoparticles (ZnONPs) and the imidacloprid (IMI) on their bioaccumulation, phytotoxicity and the underlying molecular mechanisms in lettuce. After 14 days of exposure, co-exposure to ZnONPs and IMI significantly aggravated phytotoxicity compared to individual treatments, as evidenced by greater biomass reduction, elevated oxidative stress, and intensified metabolic disruptions. Additionally, mixture treatments significantly increased both Zn and IMI accumulation in shoots, indicating enhanced uptake and upward translocation due to their coexistence. The biotransformation of IMI into 5-OH-IMI was enhanced by ZnONPs by 5.8–130 % in lettuce, with the magnitude depending on particle size and IMI concentration. For the comparison between different particle sizes, 90 nm ZnONPs led to higher Zn and IMI accumulation in shoots, whereas 30 nm ZnONPs more efficiently enhanced IMI metabolism. These accumulation patterns were closely linked to the distinct metabolic reprogramming. Co-exposure uniquely activated pathways related to amino acid and energy metabolism, indicating increased amino acid turnover and elevated energy demand for detoxification and damage repair. Altogether, the findings provide new mechanistic insights into nanoparticle–pesticide interactions in edible plants and emphasize the need to consider co-contaminant scenarios in environmental risk assessment.