Bioactive Materials

Bioactive Materials

Volume 10, April 2022, Pages 117-130
Bioactive Materials

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

https://doi.org/10.1016/j.bioactmat.2021.08.012Get rights and content
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Highlights

  • Assembled Au@Ce NPs exhibited multi-enzyme activity and the high-performance SOD-like activity even upon the oxidation of H2O2.

  • In the assembled Au@Ce NPs, Ce NPs can acquire the electrons from Au NPs to maintain the stability of Ce3+/Ce4+ and SOD activity.

  • Au@Ce can scavenge O2•- and the derived ROS in AML cells to arrest cell cycle signal and proliferation signal.

  • Au@Ce treatment suppressed the growth of HL-60 bearing tumors and prolonged the survival time in systemic AML mice.

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.

Graphical abstract

Au@CeO2 NPs, assembled by Au NPs and CeO2 NPs, eliminated ROS signaling and arrested cell cycle and proliferation through its high-performance SOD activity and the relay conversion of O2•- →H2O2→O2. (i) Schematic of CeO2 NPs SOD activity that was suppressed by the oxidation of H2O2. (ii) Schematic of Au@CeO2 NPs SOD activity that can maintain the stability against the oxidation of H2O2 according to the electron compensation effect from Au substrate.

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Keywords

Superoxide dismutase
Au nanoparticles
CeO2 nanoparticles
Reactive oxygen species
Acute myeloid leukemia

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Peer review under responsibility of KeAi Communications Co., Ltd.

1

Yuxiang Sun, Xin Liu and Lei Wang contributed equally to this work.