Persistent Regulation of Tumor Microenvironment via Circulating Catalysis of MnFe2O4@Metal–Organic Frameworks for Enhanced Photodynamic Therapy

Abstract Reactive oxygen species (ROS)‐based cancer therapy, such as photodynamic therapy (PDT), is subject to the hypoxia and overexpressed glutathione (GSH) found in the tumor microenvironment (TME). Herein, a novel strategy is reported to continuously and simultaneously regulate tumor hypoxia and reducibility in order to achieve the desired therapeutic effect. To accomplish this, a biocompatible nanoplatform (MnFe 2 O 4 @metal–organic framework (MOF)) is developed by integrating a coating of porphyrin‐based MOF as the photosensitizer and manganese ferrite nanoparticle (MnFe 2 O 4 ) as the nanoenzyme. The synthetic MnFe 2 O 4 @MOF nanoplatform exhibits both catalase‐like and glutathione peroxidase‐like activities. Once internalized in the tumor, the nanoplatform can continuously catalyze H 2 O 2 to produce O 2 to overcome the tumor hypoxia by cyclic Fenton reaction. Meanwhile, combined with the Fenton reaction, MnFe 2 O 4 @MOF is able to persistently consume GSH in the presence of H 2 O 2 , which decreases the depletion of ROS upon laser irradiation during PDT and achieves better therapeutic efficacy in vitro and in vivo. Moreover, the nanoplatform integrates a treatment modality with magnetic resonance imaging, along with persistent regulation of TME, to promote more precise and effective treatment for future clinical application.