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 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 encapsu-lating 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 ex-plains 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 anti-cancer mechanism for effective tumor ablation with enough safety.This work provides insights into the developments of MOF-based heterojunctions as powerful anticancer treatment nanoreactors.