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

Abstract

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.

Adverse Responses following Exposure to Subtoxic Concentrations of Zinc Oxide and Nickle Oxide Nanoparticles in the Raw 264.7 Cells

“…It is worth mentioning that previous studies have shown that exposure to a wide range of inorganic ENMs, including titanium dioxide, gold, silver, and copper nanoparticles, could be associated with perturbations of basic metabolic pathways such as those involved in bioenergetics, biosynthesis, and redox reactions in different experimental models [ 33 , 34 , 35 , 36 ]. Furthermore, it has been demonstrated that exposure to ENMs could disturb key cellular pathways, including apoptosis, ferroptosis, redox homeostasis, energy metabolism, mitochondrial function, and inflammatory responses [ 49 , 50 , 51 ]. To the best of our knowledge, this is the first study that assessed metabolomic changes at low and subtoxic concentrations of ZnONPs and NiONPs.…”

Review on analytical technologies and applications in metabolomics

“…Another advantage of metabolomics is that information on a large number of metabolites could be obtained through a single measurement, an oftentimes-basic requirement for rapidly understanding the level of drug toxicity. A large-scale screening of drugs or chemical compounds can be achieved through in vitro metabolomics approaches [169][170][171].…”

“…One important use of in vitro metabolomics, which employs cell lines, primary cells, co-cultures in 2D or 3D format, etc., is to predict toxicological patterns of unknown chemicals in the biological system using known reference chemicals [170,172]. Such analysis starts with the comparison of a metabolic profile of a known reference chemical with its toxicological profile in vivo.…”