Integrated metabolomics revealed the photothermal therapy of melanoma by Mo₂C nanosheets: toward rehabilitated homeostasis in metabolome combined lipidome

Melanoma, the most aggressive and life-threatening form of skin cancer, lacks innovative therapeutic approaches and deeper bioinformation. In this study, we developed a photothermal therapy (PTT) based on Mo₂C nanosheets to eliminate melanoma while utilizing integrated metabolomics to investigate the metabolic shift of metabolome combined lipidome during PTT at the molecular level. Our results demonstrated that 1 mg ml⁻¹ Mo₂C nanosheets could efficiently convert laser energy into heat with a strong and stable photothermal effect (74 ± 0.9 °C within 7 cycles). Furthermore, Mo₂C-based PTT led to a rapid decrease in melanoma volume (from 3.299 to 0 cm²) on the sixth day, indicating the effective elimination of melanoma. Subsequent integrated metabolomics analysis revealed significant changes in aqueous metabolites (including organic acids, amino acids, fatty acids, and amines) and lipid classes (including phospholipids, lysophospholipids, and sphingolipids), suggesting that melanoma caused substantial fluctuations in both metabolome and lipidome, while Mo₂C-based PTT helped improve amino acid metabolism-related biological events (such as tryptophan metabolism) impaired by melanoma. These findings suggest that Mo₂C nanosheets hold significant potential as an effective therapeutic agent for skin tumors, such as melanoma. Moreover, through exploring multidimensional bioinformation, integrated metabolomics technology provides novel insights for studying the metabolic effects of tumors, monitoring the correction of metabolic abnormalities by Mo₂C nanosheet therapy, and evaluating the therapeutic effect on tumors. © 2024 The Royal Society of Chemistry.