HBO helps CuET@PH NPs interrupt TCA cycle in Panc02 CSCs. KEGG-enriched pathway analysis based on metabolite differences between hypoxia and hypoxia combined with 0.03 μg/ml CuET@PH (A) as well as between HBO and HBO combined with 0.03 μg/ml CuET@PH (C). Up- and down-regulation of metabolites in volcano plots of hypoxia versus hypoxia combined with CuET@PH (B) and HBO versus HBO combined with CuET@PH (D), based on targeted metabolomic analysis (n = 6, FC ≥ 2, VIP ≥ 1). OCR of Panc02 CSCs in hypoxia (E) and HBO (F) after 24 hours of 0.07 μg/ml CuET@PH treatment (Oligo, oligomycin; FCCP, carbonylcyano-4-trifluoromethoxyphenylhydrazone; Rot/Ant, rotenone/antimycin A) (mean ± SEM, n = 4). (G) WB analysis of Panc02 CSCs treated with different concentrations of CuET@PH in hypoxia or HBO for 24 h. (H) PDH enzyme activity of Panc02 CSCs treated with different concentrations of CuET@PH in hypoxia or HBO for 24 h. Statistical significance was calculated by t test. **P < 0.01, ***P < 0.001.