A cascade-reaction enabled synergistic cancer starvation/ROS-mediated/chemo-therapy with an enzyme modified Fe-based MOF

Synergistic cancer starvation/ROS-mediated/chemo-therapy is developed through a cascade reaction with enzyme glucose oxidase (GOX) modified on the surface of an Fe-based metal organic framework (MOF(Fe)) and drug camptothecin (CPT) loaded into the cavities of MOF(Fe). Once internalized by tumor cells, GOX catalyzes endogenous glucose into hydrogen peroxide (H₂O₂) and gluconic acid (H⁺) enabling starvation therapy through choking off energy (glucose) supply. Meanwhile, the acidic micro-environment of tumor enhanced by the generated H⁺ degrades the MOF(Fe) simultaneously releasing CPT for chemotherapy and Fe³⁺, catalyzing H₂O₂ into one of the strongest reactive oxygen species (ROS) OH enabling ROS-mediated therapy. Both in vitro and in vivo results show remarkable tri-modal synergistic anticancer effects. This work may shed some light on the development of novel multi-modal cancer therapies without any external intervention.