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

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.