Zinc oxide nanoparticles confer tolerance to cadmium stress in Nicotiana plants by modulating melatonin-mediated defense response and metabolic reprogramming

Cadmium (Cd) contamination is increasingly recognized as a substantial threat to human health and ecosystems. Zinc oxide nanoparticles (ZnNPs) function directly in many aspects of plant stress responses, but the role of ZnNPs under Cd stress, and corresponding underlying mechanisms, remain unclear. Here, we found that ZnNPs priming effectively inhibited the oxidative damage and alleviated the photoinhibition in tobacco plants exposed to Cd stress. The application of ZnNPs enhanced Cd tolerance by protecting chloroplast integrity, raising activities of antioxidant enzyme, modulating phytohormone levels, and decreasing the downregulation of photosynthesis-related genes upon Cd exposure. These effects were closely related to the ability of ZnNPs to supply zinc and promote endogenous melatonin (MT) biosynthesis, thereby reducing Cd uptake by roots and its translocation to leaves via transporter genes expression. Integrated transcriptomic and metabolomic analyses revealed that ZnNPs modulated several key metabolic pathways, including amino acid metabolism and phenylpropanoid biosynthesis, thereby increasing the enrichment of beneficial metabolites. Compared with the Cd control, exogenous MT application under Cd conditions increased leaf photosynthesis by 90.6%, plant dry biomass by 14.3 % to 37.8%, and the chlorophyll content by 17.4 to 49.6%, indicating that Cd tolerance is associated with the regulation of MT metabolism. Collectively, our findings provide a more comprehensive understanding of ZnNPs-induced Cd tolerance and highlight its potential application in promoting sustainable agriculture.