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

Abstract

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 H2O2 and O2 in the tumor microenvironment. In this study, a CaO2@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 (CaO2) nanoparticles (NPs) to form CaO2@DOX, which was then encapsulated in a copper zeolitic imidazole ester MOF (Cu/ZIF-8) to form CaO2@DOX@Cu/ZIF-8 NPs. In the mildly acidic tumor microenvironment, CaO2@DOX@Cu/ZIF-8 NPs rapidly disintegrated, releasing CaO2, which reacted with water to generate H2O2 and O2 in the tumor microenvironment. The ability of CaO2@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 CaO2@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.