Engineered Nanozymes with Asymmetric Mn─O─Ce Sites for Intratumorally Leveraged Multimode Therapy

Abstract

Abstract Due to the enhanced flexibility of catalytic sites and synergistic effects between dual‐atom active centers, dual‐atom nanozymes stand out in the tumor catalytic therapy. However, precisely regulating the d‐band centers of diatomic sites to break the linear‐scaling relationship between intermediates remains a challenge. Herein, the hydrothermally mass‐produced oxygen vacancies‐engineered bimetallic silicate bio‐nanoplatform with highly asymmetric O‐bridged cerium─manganese (Ce─Mn) diatomic catalytic centers (CeMn‐V DAs/EGCG@HA) is meticulously constructed by loading epigallocatechin‐3‐gallate (EGCG) and modifying with hyaluronic acid (HA) for multimodal synergistic cancer therapy. Theoretical calculations reveal that the introduction of Ce sites serves as secondary catalytic centers and upshifts d‐band center of the Mn sites, thereby optimizing the adsorption/desorption of oxygen intermediates. The asymmetric Mn─O─Ce moiety facilitates electron transport within CeMn‐V DAs, significantly enhancing peroxidase‐like activities ( K m = 27.7 mM and V max = 3.21×10 ─7  M s ─1 ). Upon 650 nm laser irradiation, CeMn‐V DAs/EGCG inhibits heat shock protein expression, enabling mild‐photothermal ( η = 36.1%) therapy, which can productively inhibit tumor growth in vivo, with an inhibition rate of up to 96.2%. Due to the ligand‐field effect of EGCG‐Mn/Ce complexes, high‐valent metal ions are effectively reduced, sustaining an intrinsic self‐driven cocatalytic cycle reaction. Overall, the construction of highly asymmetric bridged diatomic nanozymes will further promote the deep integration of nanotechnology and biology.