X-ray-Activated Asymmetric Cobalt Single-Atom Nanozyme Potentiates Catalytic Immunotherapy via Enhanced...

Single-atom nanozymes (SAzymes) have emerged as promising platforms for catalytic therapy owing to their atomic precision and tunable electronic structures. Here, we report an asymmetrically coordinated cobalt SAzyme featuring Co-N₃C active sites anchored within a hafnium-based metal-organic framework (Hf-MOF). The engineered HfCoNC nanozyme exhibits significantly enhanced peroxidase-like activity and enables efficient X-ray-activated catalytic immunotherapy. The asymmetric Co-N₃C coordination optimizes substrate adsorption and lowers the reaction energy barrier, thereby accelerating the catalytic reaction. In the tumor microenvironment, HfCoNC efficiently converts endogenous H₂O₂ into highly cytotoxic hydroxyl radicals (•OH), while low-dose X-ray irradiation further amplifies reactive oxygen species (ROS) production. The resulting oxidative stress induces extensive DNA damage and activates the cGAS-STING signaling pathway. Moreover, the release of Co²⁺ ions, together with the co-delivered STING agonist, further potentiates systemic antitumor immunity, effectively suppressing tumor growth and metastasis. This work provides a promising strategy for developing SAzyme-based platforms for synergistic catalytic radioimmunotherapy.