Dual-responsive metal organic framework for electrically-enhanced cascade catalytic tumor therapy

Chemodynamic Therapy (CDT) based on Fenton reaction that can produce highly toxic reactive oxygen species to kill cancer cells has attracted considered attention. However, the effect of the CDT is limited in specific conditions (e.g. pH and H₂O₂ content) in tumor microenvironment (TME). In this paper, a glucose oxidase (GOx) and Fe³⁺-loaded metal organic framework system (GOx@MOF@Fe³⁺), to enhance the cascade reaction of the therapy, was developed for combined starvation therapy and CDT with the assistance of electrolysis. The GOx@MOF@Fe³⁺ in the tumor microenvironment was decomposed and thus released the Fe³⁺ and GOx. The electrolysis procedure, can not only trigger the Fe³⁺ and Fe²⁺ cyclic reactions, also provided O₂ for the oxidation and decomposition of glucose to generate H₂O₂. This resulted in the improvement of the pH in TME for Fenton reaction, to enhance the CDT treatment effect. Meanwhile, glucose and O₂ were consumed by GOx to achieve the effect of blocking nutrients. Compared with other control groups, the GOx@MOF@Fe³⁺ under electrolysis showed the considerable inhibitory effect of tumor cells, and the apoptosis rate even reached 80%. Our work presents an ingenious nanoenzyme for Fenton reactions that achieves a self-supplying strategy under electrolysis to improve anti-tumor efficacy.