Enhanced pH-Responsive Chemo/Chemodynamic Synergistic Cancer Therapy Based on In Situ Cu2+ Di-Chelation

Considering the chemodynamic therapy and chemotherapyindependentof external stimulus witnessing great advantage in the clinical translation,developing a smart nanoplatform that can realize enhanced chemo/chemodynamicsynergistic therapy in the tumor microenvironment (TME) is of greatsignificance. Herein, we highlight the enhanced pH-responsive chemo/chemodynamicsynergistic cancer therapy based on in situ Cu2+ di-chelation.The alcohol-withdrawal drug disulfiram (DSF) and chemotherapeuticdrug mitoxantrone (MTO) were embedded into PEGylated mesoporous CuO(denoted as PEG-CuO@DSF@MTO NPs). The acidic TME triggered the collapseof CuO and the concurrent release of Cu2+, DSF, and MTO.Then, the in situ complexation between Cu2+ and DSF, aswell as the coordination between Cu2+ and MTO not onlyprominently enhanced the chemotherapeutic performance but also triggeredthe chemodynamic therapy. In vivo mouse model experiments demonstratedthat the synergistic therapy can remarkably eliminate tumors. Thisstudy provides an interesting strategy to design intelligent nanosystems,which could proceed to clinical translations.