Glucose oxidase/copper‑carbon dots/hyaluronic acid self-assembly for self-supply hydrogen peroxide in a double-enzyme cascade to enhance anti-tumor therapy

Although chemodynamic therapy (CDT) has proven to be a promising anti-tumor strategy, its efficacy is limited by the insufficient supply of H₂O₂ in tumor tissues. To solve the problem of insufficient H₂O₂, in this paper, a novel double-enzyme cascade nanoreactor hyaluronic-cinnamaldehyde Schiff base@glucose oxidase (GOx)/copper doped carbon dot (abbreviation HCFCTG), which constructed by co-assembly of copper doped carbon dot (CuFACDs-TPP), glucose oxidase (GOx) and hyaluronic-cinnamaldehyde Schiff base (HA-CA) was designed for the first time. The HCFCTG released GOx and CuFACDs-TPP under pH stimulation. GOx continues to supply H₂O₂ to CDT by consuming glucose, while cutting off the supply of nutrients to starve cancer cells to death (ST), ultimately amplifying the therapeutic effect of CDT. CuFACDs-TPP precisely anchors mitochondria to destroy mitochondria and induce apoptosis, while copper ions consume glutathione to amplify reactive oxygen species (ROS) levels. Self‑oxygenation of HCFCTG by Fenton-like reaction down-regulates hypoxia-inducible factor (HIF-1α) to consolidate CDT effect. The 808 nm laser activates the photothermal effect enhances CDT. In vitro and in vivo experiments proved that HCFCTG has good biocompatibility and excellent CDT effect. HCFCTG overcomes the problem of insufficient H₂O₂ in the CDT process.