Coronal relay reactor Fe3O4@CeO2 for accelerating ROS axial conversion through enhanced Enzyme-like effect and relay effect

Abstract Superoxide anion (O2•-), hydrogen peroxide (H2O2), hydroxyl radical (•OH) are the main components of endogenous reactive oxygen species (ROS), while •OH shows the most significant cytotoxicity to tumor cells. Thus effective and continuous •OH generation is critical to ROS-based tumor treatment. Herein, we assembled coronal-shaped Fe3O4@CeO2 nanoparticles (NPs) to achieve relay conversion of O2•- → H2O2 → •OH in acute myeloid leukemia (AML) cells, where CeO2 NPs function as the mimetic enzyme of superoxide dismutase (SOD) to convert O2•- → H2O2 and Fe3O4 NPs act as the peroxidase (POD) mimetic enzyme to realize H2O2 → •OH. We found that assembled Fe3O4@CeO2 got an enhanced POD activity and SOD activity due to the mechanism of more efficient relay conversion at sub-nanometer distance. As a result, assembled Fe3O4@CeO2 successfully promoted the relay conversion of O2•- → H2O2 → •OH in vitro and in AML cells, causing a continuous generation of •OH by utilizing the oxygen source of endogenous O2•- and endogenous H2O2. In AML cells, reportedly, O2•- and H2O2 were both in high levels and the generation of O2•- is sustainable. Furthermore, Fe3O4@CeO2-driven the endogenous ROS axial conversion exacerbated AML cells apoptosis and prolonged the survival time of systemic AML mice, showing the worth of this relay conversion mechanism. Therefore, assembled Fe3O4@CeO2 provides an ideal tool for the directed conversion of intracellular ROS and continuous generation of •OH. Importantly, the targeted conversion of ROS by assembling multi-enzyme system is an effective strategy for the intervention of ROS.