Development of the Cu/ZIF-8 MOF Acid-Sensitive Nanocatalytic Platform Capable of Chemo/Chemodynamic Therapy with Improved Anti-Tumor Efficacy

[Image: see text] Recently, the combination of chemotherapy and chemodynamic therapy (CDT) has become a desirable strategy in the treatment of cancer. However, a satisfactory therapeutic outcome is often difficult to achieve due to the deficiency of endogenous H(2)O(2) and O(2) in the tumor microenvironment. In this study, a CaO(2)@DOX@Cu/ZIF-8 nanocomposite was prepared as a novel nanocatalytic platform to enable the combination of chemotherapy and CDT in cancer cells. The anticancer drug doxorubicin hydrochloride (DOX) was loaded onto calcium peroxide (CaO(2)) nanoparticles (NPs) to form CaO(2)@DOX, which was then encapsulated in a copper zeolitic imidazole ester MOF (Cu/ZIF-8) to form CaO(2)@DOX@Cu/ZIF-8 NPs. In the mildly acidic tumor microenvironment, CaO(2)@DOX@Cu/ZIF-8 NPs rapidly disintegrated, releasing CaO(2), which reacted with water to generate H(2)O(2) and O(2) in the tumor microenvironment. The ability of CaO(2)@DOX@Cu/ZIF-8 NPs to combine chemotherapy and CDT was assessed by conducting cytotoxicity, living dead staining, cellular uptakes, H&E staining, and TUNEL assays in vitro and in vivo. The combination of chemotherapy and CDT of CaO(2)@DOX@Cu/ZIF-8 NPs had a more favorable tumor suppression effect than the nanomaterial precursors, which were not capable of the combined chemotherapy/CDT.