Catalase-like metal–organic framework nanoparticles to enhance radiotherapy in hypoxic cancer and prevent cancer recurrence

Tumor hypoxia typically occurs inside a solid tumor with an inadequate oxygen supply, sharply reducing the therapeutic efficiency of radiotherapy and significantly increasing the risk of local tumor recurrence. Herein, we designed folic acid modified enzyme-like hafnium-based manganoporphyrin metal–organic framework nanoparticles (MnTCPP–Hf–FA MOF NPs) to overcome hypoxia-induced radioresistance and prevent postoperative recurrence. Hf, a high-Z element, can effectively absorb X-ray energy and convert O(2) and H(2)O into reactive oxygen species to induce cell apoptosis. The MnTCPP ligand has an enzyme-like ability to catalytically decompose endogenous H(2)O(2) into O(2) for enhancing RT in hypoxic tumors. In vivo experiments revealed that the MOF NPs could effectively inhibit melanoma growth and prevent tumor postoperative recurrence with only one X-ray irradiation after intravenous injection. We expect that the current study provides a versatile approach for solving the critical radioresistance issue of hypoxic tumors.