A Cerium Vanadate Nanozyme with Specific Superoxide Dismutase Activity Regulates Mitochondrial Function and ATP Synthesis in Neuronal Cells

Abstract Nanoparticles that functionally mimic the activity of metal‐containing enzymes (metallo‐nanozymes) are of therapeutic importance for treating various diseases. However, it is still not clear whether such nanozymes can completely substitute the function of natural enzymes in living cells. In this work, we show for the first time that a cerium vanadate (CeVO 4 ) nanozyme can substitute the function of superoxide dismutase 1 and 2 (SOD1 and SOD2) in the neuronal cells even when the natural enzyme is down‐regulated by specific gene silencing. The nanozyme prevents the mitochondrial damage in SOD1‐ and SOD2‐depleted cells by regulating the superoxide levels and restores the physiological levels of the anti‐apoptotic Bcl‐2 family proteins. Furthermore, the nanozyme effectively prevents the mitochondrial depolarization, leading to a significant improvement in the cellular levels of ATP under oxidative stress.