Assembled Au@Ce NPs exhibited multi-enzyme activity and the high-performance SOD-like activity even upon the oxidation of H2O2.
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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.
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Au@Ce can scavenge O2•- and the derived ROS in AML cells to arrest cell cycle signal and proliferation signal.
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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.
Keywords
Superoxide dismutase
Au nanoparticles
CeO2 nanoparticles
Reactive oxygen species
Acute myeloid leukemia
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