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.