Cu²⁺ -Anchored Carbon Nano-Photocatalysts for Visible Water Splitting to Boost Hydrogen Cuproptosis

Both hydrogen (H₂ ) and copper ions (Cu⁺ ) can be used as anti-cancer treatments. However, the continuous generation of H₂ molecules and Cu⁺ in specific sites of tumors is challenging. Here we anchored Cu²⁺ on carbon photocatalyst (Cu@CDCN) to allow the continuous generation of H₂ and hydrogen peroxide (H₂ O₂ ) in tumors using the two-electron process of visible water splitting. The photocatalytic process also generated redox-active Cu-carbon centers. Meanwhile, the Cu²⁺ residues reacted with H₂ O₂ (the obstacle to the photocatalytic process) to accelerate the two-electron process of water splitting and cuprous ion (Cu⁺ ) generation, in which the Cu²⁺ residue promoted a pro-oxidant effect with glutathione through metal-reducing actions. Both H₂ and Cu⁺ induced mitochondrial dysfunction and intracellular redox homeostasis destruction, which enabled hydrogen therapy and cuproptosis to inhibit cancer cell growth and suppress tumor growth. Our research is the first attempt to integrate hydrogen therapy and cuproptosis using metal-enhanced visible solar water splitting in nanomedicine, which may provide a safe and effective cancer treatment.