MOFs‐Based Magnetic Nanozyme to Boost Cascade ROS Accumulation for Augmented Tumor Ferroptosis

Abstract The emerging cell death modality of ferroptosis has garnered increasing attention for antitumor treatment but still suffers from low therapeutic efficacy. A metal–organic frameworks (MOFs)‐based magnetic nanozyme (PZFH) comprising porphyrin‐based Zr‐MOF (PCN) on zinc ferrite (ZF) nanoparticles modified with hyaluronic acid, delivering excellent magnetophotonic response for efficient ferroptosis, is reported here. PZFH shows multienzyme‐like cascade activity encompassing a photon‐triggered oxidase‐like catalysis to generate O 2 − , which is converted to H 2 O 2 by superoxide dismutase‐like activity and subsequent ·OH by magneto‐promoted peroxidase (POD) behavior. Newly formed Fe─N coordination and increased Fe 2+ /Fe 3+ levels in the PZFH contribute to the enhanced POD activity, which is further enhanced by accelerated surface electron transfer when exposure to alternated magnetic field. Accumulation of lipid peroxides is eventually accomplished through the conversion of ·OH radicals and singlet oxygen ( 1 O 2 ) produced through laser irradiation. When combined with the depletion of inhibition of glutathione and glutathione peroxidase 4, PZFH exhibits significantly enhanced ferroptosis in tumor‐bearing mice, offering insights into nanomedicine for ferroptosis and holding great promise in clinical antitumor therapies.