High-performance SOD mimetic enzyme Au@Ce for arresting cell cycle and proliferation of acute myeloid leukemia

SOD-like activity of CeO_(2) nanoparticles(Ce NPs)is driven by Ce^(3+)/Ce^(4+),high oxidative stress can oxidize Ce^(3+) to reduce the ratio of Ce^(3+)/Ce^(4+),inactivating the SOD activity of Ce NPs.Herein,we found Au@Ce NPs,assembled by Au NPs and Ce NPs,exhibited high-performance of SOD mimetic enzyme activity even upon the oxidation of H_(2)O_(2).Ce NPs supported by nano-Au can acquire the electrons from Au NPs through the enhanced localized surface plasmon resonance(LSPR),maintaining the stability of Ce^(3+)/Ce^(4+) and SOD-like activity.Meanwhile,Au@Ce NPs retained the peroxidase function and catalase function.As a result,Au@Ce NPs effectively scavenged O_(2·-) and the derived ROS in AML cells,which are the important signaling source that drives AML cell proliferation and accelerates cell cycle progression.When HL-60 cells were treated by Au@Ce NPs,the removal of endogenous ROS signal significantly arrested cell cycle at G1 phase and suppressed the cell proliferation by blocking the mitogen-activated protein kinases(MAPKs)signaling and the Akt/Cyclin D1 cell cycle signaling.Importantly,this treatment strategy showed therapeutic effect for subcutaneous transplantation of AML model as well as a satisfactory result in diminishing the leukocyte infiltration of liver and spleen particularly.Thus,assembled Au@Ce NPs show the high-performance SOD-like activity,promising the potential in treating AML and regulating abnormal ROS in other diseases safely and efficiently.