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

• A novel MOF-based binary heterojunction FMG has been fabricated. • Heterojunction strategy endows FMG with anti-tumor intelligence for the first time. • FMG achieved the enhanced chemodynamic/starvation therapy with enough safety. 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 Fe 3 O 4 @MIL-100 heterojunction by growing Fe-based metal-organic framework (MIL-100) onto the surface of Fe 3 O 4 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 H 2 O 2 and gluconic acid further improve the CDT efficiency. More O 2 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. [Display omitted] [ABSTRACT FROM AUTHOR]