Development of an intelligent heterojunction fenton catalyst for chemodynamic/starvation synergistic cancer therapy

Chemodynamic therapy (CDT) as an emerging modality in cancer treatment, its implementation remains a daunting challenge by the lack of smart Fenton catalyst under acidic tumor microenvironments. Herein, we have successfully constructed a Fe3O4@MIL-100 heterojunction by growing Fe-based metal-organic framework (MIL-100) onto the surface of Fe3O4 nanoparticles. The as-made heterojunction after encapsulating glucose oxidase (termed FMG) is demonstrated as a pH-responsive intelligent Fenton nanosystem with the synergistic effect of starvation therapy (ST). Density functional theory (DFT) calculations reveal that such heterojunction could greatly reduce the energy barrier of the Fenton reaction, which better explains the mechanism of Fenton performance improvement. Moreover, the encapsulated glucose oxidase has successfully activated the ST process, in which its generated H2O2 and gluconic acid further improve the CDT efficiency. More O2 from the enhanced CDT in turn promotes the enzymatic reaction of glucose oxidase. The Fenton/cascade enzymatic reaction operates in a self-feedback manner as proposed. In vitro and in vivo experiments demonstrate that such intelligent Fenton nanoreactors provide a powerful anticancer mechanism for effective tumor ablation with enough safety. This work provides insights into the developments of MOF-based heterojunctions as powerful anticancer treatment nanoreactors.