Self-Supply of O2 and H2O2 by a Nanocatalytic Medicine to Enhance Combined Chemo/Chemodynamic Therapy

Abstract

Combined chemo/chemodynamic therapy is a promising strategy to achieve an improved anticancer effect. However, the hypoxic microenvironment and limited amount of H2O2 in most solid tumors severely restrict the efficacy of this treatment. Herein, the construction of a nanocatalytic medicine, CaO2@DOX@ZIF-67, via a bottom-up approach is described. CaO2@DOX@ZIF-67 simultaneously supplies O2 and H2O2 to achieve improved chemo/chemodynamic therapy. In the weakly acidic environment within tumors, CaO2@DOX@ZIF-67 is broken down to rapidly release the Fenton-like catalyst Co2+ and the chemotherapy drug doxorubicin (DOX). The unprotected CaO2 reacts with H2O to generate both O2 and H2O2. The generated O2 relieves the hypoxia in the tumor and further improve the efficacy of DOX. Meanwhile, the generated H2O2 reacts with Co2+ ions to produce highly toxic •OH through a Fenton-like reaction, resulting in improved chemodynamic therapy.