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

Superoxide anion (O-2 center dot-), hydrogen peroxide (H2O2), hydroxyl radical (center dot OH) are the main components of endogenous reactive oxygen species (ROS), while center dot OH shows the most significant cytotoxicity to tumor cells. Thus effective and continuous center dot OH generation is critical to ROS-based tumor treatment. Herein, we assembled coronal-shaped Fe3O4@CeO2 nanoparticles (NPs) to achieve relay conversion of O-2 center dot- -> H2O2 -> center dot OH in acute myeloid leukemia (AML) cells, where CeO2 NPs function as the mimetic enzyme of superoxide dismutase (SOD) to convert O-2 center dot- -> H2O2 and Fe3O4 NPs act as the peroxidase (POD) mimetic enzyme to realize H2O2 -> center dot OH. We found that assembled Fe3O4@CeO(2 )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 O-2 center dot- -> H2O2 -> center dot OH in vitro and in AML cells, causing a continuous generation of center dot OH by utilizing the oxygen source of endogenous O-2 center dot- and endogenous H2O2. In AML cells, reportedly, O-2 center dot- and H2O2 were both in high levels and the generation of O-2 center dot- 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 center dot OH. Importantly, the targeted conversion of ROS by assembling multi-enzyme system is an effective strategy for the intervention of ROS.

Automated summary

The study successfully assembled coronal-shaped Fe3O4@CeO2 nanoparticles for relay conversion of O-2 center dot- -> H2O2 -> center dot OH in AML cells, enhancing ROS generation and impact on AML cells. The targeted conversion of ROS by assembling multi-enzyme system is an effective strategy for the intervention of ROS.