Development of the Cu/ZIF-8 MOF Acid-Sensitive Nanocatalytic Platform Capable of Chemo/Chemodynamic Therapy with Improved Anti-Tumor Efficacy
Jie Liang, Weiwei Zhang, Jun Wang, Wanzhen Li, Fei Ge, Weihao Jin, Yugui Tao
Abstract
High Resolution Image Download MS PowerPoint Slide 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 @ [email protected] /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 @ [email protected] /ZIF-8 NPs. In the mildly acidic tumor microenvironment, CaO 2 @ [email protected] /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 @ [email protected] /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 @ [email protected] /ZIF-8 NPs had a more favorable tumor suppression effect than the nanomaterial precursors, which were not capable of the combined chemotherapy/CDT.