Phosphate-Degradable Nanoparticles Based on Metal-Organic Frameworks for Chemo-Starvation-Chemodynamic Synergistic...

Chemodynamic therapy (CDT) was regarded as a promising approach for tumor treatment. However, owing to the insufficient amount of endogenous hydrogen peroxide (H₂O₂) in tumor cells, the efficacy of CDT was limited. In this study, we designed phosphate-responsive nanoparticles (denoted as MGDFT NPs) based on metal-organic frameworks, which were simultaneously loaded with drug doxorubicin (DOX) and glucose oxidases (GOx). The decorated GOx could act as a catalytic nanomedicine for the response to the abundant glucose in the tumor microenvironment, generating a great deal of H₂O₂, which would enhance the Fenton reaction and produce toxic hydroxyl radicals (·OH). Meanwhile, the growth of tumors would also be inhibited by overconsuming the intratumoral glucose, which was the "fuel" for cell proliferation. When the nanoparticles entered into tumor cells, a high concentration of phosphate induced structure collapse, releasing the loaded DOX for chemotherapy. Furthermore, the decoration of target agents endowed the nanoparticles with favorable target ability to specific tumor cells and mitochondria. Consequently, the designed MGDFT NPs displayed desirable synergistic therapeutic effects via combining chemotherapy, starvation therapy, and enhanced Fenton reaction, facilitating the development of multimodal precise antitumor therapy.