Proteomics and Metabolomics Analysis Reveals the Toxicity of ZnO Quantum Dots on Human SMMC-7721 Cells

PURPOSE: ZnO quantum dots (QDs) are composed of less toxic metals than other QDs but have the same interesting photochemical properties. Thus, they have received considerable attention recently. Nevertheless, their toxicity cannot be ignored. METHODS: In this study, we incubated ZnO QDs with human SMMC-7721 cells for 24 h to assess their nanotoxicity through proteomics (Fold change >1.5 and p-value <0.05) and metabolomics (Fold change ≥ 1.5; VIP ≥ 1; p-value < 0.05) analyses. RESULTS: Both of 174 and 219 significantly changed metabolites were identified in human SMMC-7721 cells treated with 20 and 50 µg/mL ZnO QDs, respectively. ZnO QDs significantly modified metabolic pathways, including purine metabolism, ferroptosis, morphine addiction, alcoholism, cGMP-PKG signaling, and Cushing syndrome. Moreover, we identified 105 and 8 differentially expressed proteins in cells treated with 20 and 50 µg/mL ZnO QDs, and the pathways of alcoholism and Cushing syndrome were enriched. CONCLUSION: ZnO QDs did not affect cell viability in a CCK8 assay, but disturbed the level of intracellular metabolites and proteins at 20 µg/mL. The KEGG analyses of the metabolomics and proteomics data both enriched the alcoholism and Cushing syndrome pathways. These results provide an experimental basis for future research on the safe use of nanomaterials.