Regulating Manganese-Site Electronic Structure via Reconstituting Nitrogen Coordination for Efficient Non-Oxygen-Dependent Sonocatalytic Therapy against Orthotopic Breast Cancer

Sonocatalytic therapy (SCT) has emerged as a promising noninvasive modality for tumor treatment but is hindered by the insufficient generation of ultrasound-induced reactive oxygen species (ROS) and the hypoxic tumor microenvironments. Herein, we fabricated a carbon nanoframe-confined N-coordinated manganese single-atom sonocatalyst with a five-coordinated structure (MnN 5 SA/CNF) using a phthalocyanine-mediated pyrolysis strategy. The precise coordination structure was identified by synchrotron X-ray absorption fine structure analyses. The MnN 5 SA/CNF exhibits superior and nonoxygen-dependent sonocatalytic activity owing to the optimized coordination structure and cavitation effect enhanced by defects. Additionally, density functional theory studies reveal that the five-coordination structure downshifts the d-band center of Mn from −0.547 to −0.829 eV and enhances the desorption capacity for oxygen-containing intermediates, thus accelerating the catalytic process. Finally, the as-synthesized MnN 5 SA/CNF demonstrates a significantly enhanced antitumor effect through mitochondrial apoptosis in an orthotopic breast cancer mouse model. This work explores the potential of SAzymes-supported biomedical interventions by leveraging enzymatic activity with sonocatalytic properties.