Sun Yuxiang, Liu Xin, Wang Lei, Xu Li, Liu Kunliang, Xu Lei, Shi Fangfang, Zhang Yu, Gu Ning, Xiong Fei
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.
Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, PR China.
Bioact Mater. 2021 Aug 18;10:117-130. doi: 10.1016/j.bioactmat.2021.08.012. eCollection 2022 Apr.
SOD-like activity of CeO nanoparticles (Ce NPs) is driven by Ce/Ce, high oxidative stress can oxidize Ce to reduce the ratio of Ce/Ce, 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 HO. 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/Ce and SOD-like activity. Meanwhile, Au@Ce NPs retained the peroxidase function and catalase function. As a result, Au@Ce NPs effectively scavenged O•- 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.
二氧化铈纳米颗粒（Ce NPs）的超氧化物歧化酶（SOD）样活性由Ce³⁺/Ce⁴⁺驱动，高氧化应激可将Ce³⁺氧化为Ce⁴⁺，从而降低Ce³⁺/Ce⁴⁺的比例，使Ce NPs的SOD活性失活。在此，我们发现由金纳米颗粒（Au NPs）和Ce NPs组装而成的Au@Ce NPs即使在过氧化氢（HO）氧化的情况下仍表现出高性能的超氧化物歧化酶模拟酶活性。纳米金负载的Ce NPs可以通过增强的局域表面等离子体共振（LSPR）从Au NPs获得电子，维持Ce³⁺/Ce⁴⁺的稳定性和SOD样活性。同时，Au@Ce NPs保留了过氧化物酶功能和过氧化氢酶功能。结果，Au@Ce NPs有效地清除了急性髓系白血病（AML）细胞中的超氧阴离子（O•-）及其衍生的活性氧（ROS），这些是驱动AML细胞增殖和加速细胞周期进程的重要信号源。当用Au@Ce NPs处理HL-60细胞时，内源性ROS信号的消除显著使细胞周期停滞在G1期，并通过阻断丝裂原活化蛋白激酶（MAPKs）信号通路和Akt/细胞周期蛋白D1细胞周期信号通路抑制细胞增殖。重要的是，这种治疗策略对AML模型的皮下移植显示出治疗效果，并且在减少肝脏和脾脏的白细胞浸润方面也取得了令人满意的结果。因此，组装的Au@Ce NPs表现出高性能的SOD样活性，有望在安全有效地治疗AML和调节其他疾病中的异常ROS方面具有潜力。
