In Situ Formed Z‑Scheme Graphdiyne Heterojunction Realizes NIR-Photocatalytic Oxygen Evolution and Selective Radiosensitization for Hypoxic Tumors

Photon radiotherapy is a common tool in the armory against tumors, but it is limited by hypoxia-related radioresistance of tumors and radiotoxicity to normal tissues. Here, we constructed a spatiotemporally controlled synergistic therapy platform based on the heterostructured CuO@Graphdiyne (CuO@GDY) nanocatalyst for simultaneously addressing the two key problems above in radiotherapy. First, the in situ formed Z-scheme CuO@GDY heterojunction performs highly efficient and controlled photocatalytic O2 evolution upon near-infrared (NIR) laser stimulation for tumor hypoxia alleviation. Subsequently, the CuO@GDY nanocatalyst with X-ray-stimulated Cu+ active sites can accelerate Fenton-like catalysis of ·OH production by responding to endogenous H2O2 for the selective killing of tumor cells rather than normal cells. In this way, the sequential combination of NIR-triggered photocatalytic O2 production and X-ray-accelerated Fenton-like reaction can lead to a comprehensive radiosensitization. Overall, this synergism underscores a controllable and precise therapy modality for simultaneously unlocking the hypoxia and non-selectivity in radiotherapy.