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 

作者机构：State Key Laboratory of BioelectronicsJiangsu Key Laboratory for Biomaterials and DevicesSchool of Biological Science and Medical Engineering&Collaborative Innovation Center of Suzhou Nano-Science and TechnologySoutheast UniversityNanjing210096PR China Department of GastroenterologyNanjing Drum Tower HospitalAffiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjingPR China Jiangsu Key Laboratory of Molecular MedicineMedical School of Nanjing UniversityNanjing210093PR China Department of Research and DevelopmentJinan Guoke Medical Technology Development Co.Ltd.Address:No.1Gangxing 3rd RoadHigh-tech Industrial Development ZoneJinan CityShandong Province250013PR China Department of OncologyZhongda HospitalSoutheast UniversityNanjing 210009China 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2022年第7卷第4期

页      面：117-130页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 0805[工学-材料科学与工程（可授工学、理学学位）] 10[医学] 

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. 

主　　题：Superoxide dismutase Au nanoparticles CeO_(2)nanoparticles Reactive oxygen species Acute myeloid leukemia 

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.