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

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.