biostudies-literatureUnknown16(3)Wang WRationale: The tumor microenvironment (TME), which is characterized by disordered metabolism, acidic pH, and high glutathione (GSH) and hydrogen peroxide (H2O2) levels, seriously hampers the efficacy of cancer therapy. Nanozymes with multi-enzyme activity have considerable potential to reprogram the TME and suppress tumor growth. Methods: A strategy for remodulating the TME based on a hierarchical CuO nanozyme with oxygen vacancies decorated with hyaluronic acid (HA) (CuO@HA) was developed. The enzyme activities of CuO@HA were evaluated by enzyme kinetic assays and density functional theory (DFT). The in vitro and in vivo anti-tumor effects were estimated, and the mechanism was explored using multi-omic methods. Results: CuO@HA exhibTheranostics1374-1385https://www.ebi.ac.uk/biostudies/studies/S-EPMC12679366biostudies-literatureSynergistic chemodynamic and metabolic reprogramming-based cancer therapy by CuO@HA nanozymes with oxygen vacancy.PMC12679366Yoon JHu TFeng MJia YCai YWang WSong HHu QWang YWang ZfalseSynergistic chemodynamic and metabolic reprogramming-based cancer therapy by CuO@HA nanozymes with oxygen vacancy.Rationale: The tumor microenvironment (TME), which is characterized by disordered metabolism, acidic pH, and high glutathione (GSH) and hydrogen peroxide (H2O2) levels, seriously hampers the efficacy of cancer therapy. Nanozymes with multi-enzyme activity have considerable potential to reprogram the TME and suppress tumor growth. Methods: A strategy for remodulating the TME based on a hierarchical CuO nanozyme with oxygen vacancies decorated with hyaluronic acid (HA) (CuO@HA) was developed. The enzyme activities of CuO@HA were evaluated by enzyme kinetic assays and density functional theory (DFT). The in vitro and in vivo anti-tumor effects were estimated, and the mechanism was explored using multi-omic methods. Results: CuO@HA exhib2026-01-01T00:00:00Z20262026-06-10T04:52:44.759Z2026-06-10T03:07:11.033ZS-EPMC126793664135596910.7150/thno.119806