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

Manganese oxide (MnOx) 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 MnOx 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.