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High-performance SOD Mimetic Enzyme Au@Ce For Arresting Cell Cycle And Proliferation Of Acute Myeloid Leukemia

Yuxiang Sun, Xin Liu, Lei Wang, Li Xu, Kunliang Liu, Lei Xu, Fangfang Shi, Yu Zhang, N. Gu, Fei Xiong
Published 2021 · Chemistry

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Abstract SOD-like activity of CeO2 nanoparticles (Ce NPs) is driven by Ce3+/Ce4+, high oxidative stress can oxidize Ce3+ to reduce the ratio of Ce3+/Ce4+, 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 H2O2. 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 Ce3+/Ce4+ and SOD-like activity. Meanwhile, Au@Ce NPs retained the peroxidase function and catalase function. As a result, Au@Ce NPs effectively scavenged O2•- 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.
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