Electrochemical Valence‐Regulated Biomimetic Nanozymes for Breast Cancer Metabolism Inhibition and Potentiated Catalytic Immunotherapy

ABSTRACT Manganese oxide (MnO x ) nanozymes have garnered significant attention for their ability to respond to the tumor microenvironment (TME) and stimulator of interferon genes (STING) pathway activation. However, they often suffer from a weak direct tumor‐killing capacity due to low enzymatic activity and from attenuated anti‐tumor immunity resulting from STING activation‐induced excessive programmed death‐ligand 1 (PD‐L1) expression. In this study, we fabricated MnO x nanozymes with precisely controllable valence states via electrochemical valence regulation to modulate their oxidase‐like activity. Notably, M‐MnOx, with a bulk Mn oxidation state of +3.62, a near‐surface Mn oxidation state of approximately +3.23, 19.1% oxygen vacancies, and a reduced Mn−O coordination number of 4.7, exhibited the highest oxidase‐like activity and was therefore selected for cancer therapy. This nanozyme was subsequently wrapped with a T lymphocyte membrane (TCM) to form biomimetic nanozymes (TMO). TMO efficiently targets tumors and induces immunogenic cell death via oxidase catalytic therapy, while also activating the cGAS‐STING pathway and T cells for tumor killing. Furthermore, TMO competitively binds to tumor cell highly expressed PD‐L1 to alleviate T cell immune suppression. Consequently, TMO demonstrates excellent tumor‐killing efficacy and inhibits recurrence in vivo. This research offers a new perspective for the construction of manganese‐based nanomaterials.