Regulating Manganese-Site\nElectronic Structure via\nReconstituting Nitrogen Coordination for Efficient Non-Oxygen-Dependent\nSonocatalytic Therapy against Orthotopic Breast Cancer

Sonocatalytic therapy (SCT) has emerged as a promising\nnoninvasive\nmodality for tumor treatment but is hindered by the insufficient generation\nof ultrasound-induced reactive oxygen species (ROS) and the hypoxic\ntumor microenvironments. Herein, we fabricated a carbon nanoframe-confined\nN-coordinated manganese single-atom sonocatalyst with a five-coordinated\nstructure (MnN<sub>5</sub> SA/CNF) using a phthalocyanine-mediated\npyrolysis strategy. The precise coordination structure was identified\nby synchrotron X-ray absorption fine structure analyses. The MnN<sub>5</sub> SA/CNF exhibits superior and nonoxygen-dependent sonocatalytic\nactivity owing to the optimized coordination structure and cavitation\neffect enhanced by defects. Additionally, density functional theory\nstudies reveal that the five-coordination structure downshifts the\nd-band center of Mn from −0.547 to −0.829 eV and enhances\nthe desorption capacity for oxygen-containing intermediates, thus\naccelerating the catalytic process. Finally, the as-synthesized MnN<sub>5</sub> SA/CNF demonstrates a significantly enhanced antitumor effect\nthrough mitochondrial apoptosis in an orthotopic breast cancer mouse\nmodel. This work explores the potential of SAzymes-supported biomedical\ninterventions by leveraging enzymatic activity with sonocatalytic\nproperties.