Rapid microwave-assisted synthesis of ZnMn dual-atom nanozymes for cancer catalytic immunotherapy.

Catalytic nanomedicines face a persistent trade-off between structurally defined active sites and rapid synthesis. A microwave-assisted salt-flux conversion is developed that transforms a bimetallic metal-organic framework precursor within 3 min into nitrogen-doped carbon-supported ZnMn dual-atom nanozymes (ZnMn DAzymes). Aberration-corrected HAADF-STEM and dual-edge X-ray absorption fine structure analyses support adjacent Zn-Mn sites with an N-dominated ZnMn-N6-like coordination motif. Steady-state kinetics and density functional theory calculations suggest cooperative catalysis: Zn modulates H2O2 adsorption and O-O bond activation, whereas Mn provides stronger H2O2 chemisorption and redox flexibility, jointly enhancing catalase-, peroxidase-, and oxidase-like activities. The resulting cascade decomposes H2O2, relieves hypoxia, generates reactive oxygen species, and depletes glutathione, inducing mitochondrial dysfunction, immunogenic cell death, cGAS-STING-associated signaling, dendritic-cell maturation, and effector T-cell infiltration. Glutathione-responsive Mn2+ release additionally enables activatable T1-weighted magnetic resonance contrast. Combined with αPD-L1, ZnMn DAzymes suppress primary and distal tumors by approximately 90%, reduce lung metastases by 92%, and prolong survival in 4T1 models. This work provides a rapid route to ZnMn dual-atom nanozymes for catalytic immunotherapy.