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

作　　者：Yuxiang Sun Xin Liu Lei Wang Li Xu Kunliang Liu Lei Xu Fangfang Shi Yu Zhang Ning Gu Fei Xiong 

机构地区：[1]State Key Laboratory of Bioelectronics,Jiangsu Key Laboratory for Biomaterials and Devices,School of Biological Science and Medical Engineering&Collaborative Innovation Center of Suzhou Nano-Science and Technology,Southeast University,Nanjing,210096,PR China [2]Department of Gastroenterology,Nanjing Drum Tower Hospital,Affiliated Hospital of Nanjing University Medical School,Nanjing University,Nanjing,PR China [3]Jiangsu Key Laboratory of Molecular Medicine,Medical School of Nanjing University,Nanjing,210093,PR China [4]Department of Research and Development,Jinan Guoke Medical Technology Development Co.,Ltd.,Address:No.1,Gangxing 3rd Road,High-tech Industrial Development Zone,Jinan City,Shandong Province,250013,PR China [5]Department of Oncology,Zhongda Hospital,Southeast University,Nanjing 210009,China

出　　处：《Bioactive Materials》2022年第4期117-130,共14页生物活性材料（英文）

基　　金：funded in part with the National Key Research and Development Program of China(2017YFA0205502,2017YFA0205501);the National Natural Science Foundation of China(82073804);Shandong Provincial Natural Science Foundation of China(ZR2020QE091);Scientific research foundation of Nanjing Health Commission(YKK20232);the the Fundamental Research Funds for the Central Universities(2242018K3DN30);supported by the Open Research Fund of State Key Laboratory of Bioelectronics Southeast University.

摘　　要：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.

关 键 词：Superoxide dismutase Au nanoparticles CeO_(2)nanoparticles Reactive oxygen species Acute myeloid leukemia 

分 类 号：R552[医药卫生—血液循环系统疾病]