Nanozymes-engineered metal-organic frameworks for enhanced microwave thermodynamic therapy in PDX of hepatic carcinoma

Dynamic therapy (DT) has emerged as a promising cancer therapy due to its non-invasive treatment and good spatiotemporal control. However, the efficiency of DT is restricted by several limitations, including insufficient oxygen supply, high expression of pre-tumor factors (e.g., vascular endothelial growth factor, VEGF), and insufficient and relatively weak oxidation ability of reactive oxygen species (ROS) generation. Herein, we propose an in-situ enzyme-like cascade catalysis therapeutic strategy for enhanced MW thermodynamic therapy. The as-prepared nanozymes-engineered metal-organic frameworks (Apatinib@ZIF67@PDA, AZP NCs nanozymes) achieve excellent therapeutic effects in a patient-derived xenograft (PDX) model of hepatic carcinoma. Precisely, after intravenous administration, the ZIF structure of AZP NCs nanozymes is disrupted in the acidic tumor microenvironment, which results in the release of Co (II) and the antiangiogenic agent of Apatinib (AP). Subsequently, Co (II) disproportionates H2O2 into highly oxidizing hydroxyl radicals (center dot OH) and Co (III). Meanwhile, Co (III) combined with MW can effectively alleviate tumor hypoxia by catalyzing the intratumoral H2O2 to O2, and enhance the generation of ROS. Moreover, the release of AP can downregulate the expression of VEGF, thus effectively inhibiting the tumor angiogenesis after MW thermodynamic therapy. Hence, tumor cells are eliminated completely under the action of MW thermodynamic therapy cooperative combination of AP by AZP NCs nanozymes. This work presents a catalytic strategy for MOF-based nanozymes to improve DT efficiency and provides a new insight for highly efficient anticancer approaches.