南京大学魏辉团队报道了用于动脉粥样硬化治疗的具有抗衰老活性的整合级联纳米酶。相关研究成果于2023年6月20日发表于国际一流学术期刊《德国应用化学》。

衰老细胞是动脉粥样硬化形成和成熟的关键驱动因素。减缓衰老细胞有望治疗动脉粥样硬化。在动脉粥样硬化斑块微环境中，衰老细胞与活性氧（ROS）相互作用，促进疾病发展。

该文中，研究人员假设一种具有抗衰老和抗氧化活性的级联纳米酶可以作为动脉粥样硬化的有效治疗药物。研究人员开发了一种具有超氧化物歧化酶和谷胱甘肽过氧化物酶样活性的集成级联纳米酶，命名为MSe1。所获得的级联纳米酶可以通过保护DNA免受损伤来减弱人脐静脉内皮细胞（HUVECs）的衰老。它通过消除过量产生的细胞内ROS，显著减弱巨噬细胞和HUVECs的炎症。

此外，MSe1纳米酶通过减少氧化低密度脂蛋白的内化，有效抑制巨噬细胞和HUVECs中泡沫细胞的形成。静脉给药后，MSe1纳米酶通过减少氧化应激和炎症，显著抑制载脂蛋白E缺陷（ApoE-/-）小鼠动脉粥样硬化的形成，然后减少动脉粥样硬化斑块中炎症细胞和衰老细胞的浸润。

该项研究不仅提供了一种级联纳米酶，而且表明抗衰老和抗氧化应激的结合在治疗动脉粥样硬化方面具有相当大的前景。

附：英文原文

Title: Integrated cascade nanozymes with antisenescence activities for atherosclerosis therapy

Author: Wanling Liu, Yihong Zhang, Gen Wei, Minxuan Zhang, Tong Li, Quanyi Liu, Zijun Zhou, Yan Du, Hui Wei

Issue&Volume: 2023-06-20

Abstract: Senescent cells are the critical drivers of atherosclerosis formation and maturation. Mitigating senescent cells holds promise for the treatment of atherosclerosis. In an atherosclerotic plaque microenvironment, senescent cells interact with reactive oxygen species (ROS), promoting the disease development. Here, we hypothesize that a cascade nanozyme with antisenescence and antioxidant activities can serve as an effective therapeutic for atherosclerosis. An integrated cascade nanozyme with superoxide dismutase- and glutathione peroxidase-like activities, named MSe1, is developed in this work. The obtained cascade nanozyme can attenuate human umbilical vein endothelial cells (HUVECs) senescence by protecting DNA from damage. It significantly weakens inflammation in macrophages and HUVECs by eliminating overproduced intracellular ROS. Additionally, the MSe1 nanozyme effectively inhibits foam cell formation in macrophages and HUVECs by decreasing the internalization of oxidized low-density lipoprotein. After intravenous administration, the MSe1 nanozyme significantly inhibits the formation of atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice by reducing oxidative stress and inflammation and then decreases the infiltration of inflammatory cells and senescent cells in atherosclerotic plaques. This study not only provides a cascade nanozyme but also suggests that the combination of antisenescence and antioxidative stress holds considerable promise for treating atherosclerosis.

DOI: 10.1002/anie.202304465

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202304465