Biomineralized DNA nanospheres by metal organic framework for enhanced chemodynamic therapy

Chemodynamic therapy (CDT) has emerged as an innovative treatment strategy for cancer therapy, and yet most of current systems are highly dependent on endogenous H₂O₂ for hydroxyl radical ([rad]OH) generation, leading to limited therapeutic efficacy. Therefore, it is of significant importance to develop CDT agents with efficient H₂O₂ self-supplying ability for enhanced CDT efficacy. Herein, we report metal organic framework (MOF)-biomineralized DNA nanospheres as CDT agent engineered with tumor-activable cascade reactions for boosting the intracellular H₂O₂ concentration, thus achieving remarkable antitumor outcome. As a result of tumor acid-induced dissociation of CDT agent, the released Fe²⁺/Fe³⁺ triggers Fenton reaction to produce [rad]OH and the released GOx enables to catalyze glucose into H₂O₂, which synergistically elevates the ROS level in tumor cells and induces ferroptosis. By exploitation of tumor acid-activable cascade reactions for supplying sufficient H₂O₂, our CDT agent achieves prominent therapeutic efficacy in both in vitro and in vivo assays. Our work provides a promising strategy to develop CDT agents for improved CDT efficacy.