Nanozyme-mediated cascade reaction based on metal-organic framework for synergetic chemo-photodynamic tumor therapy

Numerous biological enzymes are considered promising for tumor therapy. However, the remote control of enzymatic activity in vivo to achieve a satisfactory therapeutic effect remains challenge. Herein, we loaded chlorin e6 (Ce6) to the peroxidase-mimic metal-organic framework (MOF) MIL-100 (Ce6@MIL-100) to develop cascade-reaction nanoparticles shielded with hyaluronic acid (CMH NPs). CMH NPs and the highly expressed H₂O₂ in the tumor site underwent Fenton reaction to generate hydroxyl radical (·OH) and O₂. The produced ·OH and O₂ were used for chemodynamic therapy and alleviating hypoxia, respectively. Under near-infrared light irradiation, the Ce6-mediated photochemical effect not only generated cytotoxic singlet oxygen (¹O₂) for enhanced photodynamic therapy with additional oxygen supply, but also produced H₂O₂ to amplify the Fenton reaction. Therefore, the CMH NPs exhibited a virtuous cycle of cascade reactions. Furthermore, comprehensive experiments demonstrated that combined therapy could effectively ablate tumors. Thus, the nanozyme based on MOF realized potent chemo-photodynamic therapeutic efficacy. Overall, the nanoplatform displayed an exciting biomedical application of MOF-derived nanozyme as a versatile therapeutic agent.