Dual Enzyme Mimics Based on Metal–Ligand Cross‐Linking Strategy for Accelerating Ascorbate Oxidation and Enhancing Tumor Therapy

Abstract The development of high‐efficiency nanozymes is of great significance in the field of nanozymology, because this is one of the prerequisites for the sophisticated performance of nanozymes. Herein, the developed metal–ligand cross‐linking strategy engineers porous carbon nanorod supported ultra‐small iron carbide nanoparticles that possess excellent oxidase‐like and peroxidase‐like enzyme activities. The fabricated nanozyme can efficiently accelerate the oxidation of ascorbate (AA) to enhance cancer cells ablation efficacy. Due to the nanozyme having great surface atoms utilization ratio and large specific surface area, the AA can be rapidly and completely autoxidized within 20 min. Mechanism research demonstrates that the nanozyme's first activation of O 2 to generate superoxide free radicals (O 2 •− ) via the oxidase‐like pathway, then the O 2 •− directly oxidizes AA and produces hydrogen peroxide (H 2 O 2 ). Simultaneously, the H 2 O 2 transforms into the toxic hydroxyl radical through the peroxidase‐like pathway and induces tumor cell death. Further in vitro and in vivo assays show the significant enhancement of the anti‐tumor efficacy through AA oxidation which is catalyzed by the developed nanozyme. It is expected that this work will benefit not only the development of other efficient nanozymes, but also future advances in the field of AA oxidation induced tumor therapy.