Ultrasound-Enhanced Generation of Reactive Oxygen Species for MRI-Guided Tumor Therapy by the Fe@Fe3O4-Based Peroxidase-Mimicking Nanozyme

Reactive oxygen species (ROS)-based tumor therapy is still challenging due to limited ROS-generating efficacy. Herein, we constructed heparin-conjugated Fe@Fe3O4 NPs (Fe@Fe3O4@heparin, denoted as MNPs) as a peroxidase-mimicking nanozyme to generate ROS for tumor therapy through the combination of the ultrasound-stimulated Fenton reaction and the increased concentration of H2O2 by beta-lapachone (La) in a tumor. La was first intraperitoneally injected into mice and induced to generate a considerable quantity of H2O2 through a specific tumor reaction, which was catalyzed by MNPs to produce highly hydroxyl radicals (.OH). Furthermore, the therapy efficacy for malignant tumors could significantly be enhanced by an ultrasonic stimulation. With the help of the increased amount of H2O2 generated by La in the tumor and the enhanced peroxidase-mimicking activity of MNPs by ultrasound, MNPs manifest good therapeutic performance in a 4T1 xenograft model, which provides a strategy for enhanced nanozyme-mediated tumor therapy.