A nanoplatform with H2O2 self-supplying capability for synergistic chemo/enzyme dynamic/chemodynamic therapy of ovarian cancer

Abstract

Chemodynamic therapy (CDT) and enzyme dynamic therapy (EDT) are effective treatment methods that kill tumor cells by producing large amounts of reactive oxygen species (ROS). However, the endogenous hydrogen peroxide (H₂O₂) concentration in tumors is insufficient, limiting the production of ROS and weakening the therapeutic effects of CDT and EDT. Therefore, a nanoplatform (CeO₂@CPT@CPO) based on mesoporous cerium dioxide (CeO₂) was designed to deliver camptothecin (CPT) and chloroperoxidase (CPO), thereby achieving synergistic CDT, EDT, and pharmacological chemotherapy of ovarian cancer. CeO₂@CPT@CPO possesses peroxidase (POD) and CPO-like activities, which can catalyze H₂O₂ to produce a large amount of ROS to kill tumor cells. CPT, as a chemotherapeutic drug, can activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate H₂O₂, thereby enhancing the therapeutic efficacy of CDT and EDT. Meanwhile, CeO₂@CPT@CPO with catalase (CAT)-like activity can catalyze H₂O₂ to produce oxygen (O₂) to alleviate hypoxia in the tumor microenvironment (TME). Additionally, CeO₂@CPT@CPO is capable of depleting intracellular glutathione (GSH), thereby safeguarding the stable presence of ROS and contributing to their further accumulation. Finally, the synergistic effect of CDT, EDT, and chemotherapy leads to mitochondrial and DNA damage, which in turn promotes apoptosis of tumor cells. The potent tumor-suppressive effect of CeO₂@CPT@CPO highlights its potential for synergistic ovarian cancer therapy.