Department of Ultrasound, Shanghai East Hospital, Tongji University, Shanghai 200120, P. R. China.
Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai 200444, P. R. China.
J Mater Chem B. 2023 Mar 1;11(9):1881-1890. doi: 10.1039/d2tb02661a.
Atherosclerosis (AS), characterized by a chronic inflammatory disease, is a top cause of morbidity and disability worldwide. During the pathogenesis of AS, the leading process of inflammation highly involves a secondary event of oxidative stress, but limited antioxidants are currently available clinically due to their nonspecific effects, poor biosafety, and rapid elimination and urinary excretion as well as short retention time within plaque lesions. In this work, Prussian blue nanozymes with a strong reactive oxygen species (ROS)-scavenging ability were rationally engineered for efficient AS nanotherapy. Specifically, the obtained nanozymes with high photothermal performance could behave as potent photoacoustic imaging agents for plaque detection. In addition, these nanozymes featuring multienzyme activities could reduce the cellular ROS level, exert cytoprotective effects against ROS-mediated macrophages apoptosis, and inhibit foam cell formation, significantly boycotting AS development. The underlying mechanism was further verified by transcriptome sequencing at the cellular level and a series of immunohistochemical staining of aortic sinus sections in apoE mice. Finally, the high biocompatibility and biosafety of the engineered Prussian blue nanozymes further guarantee their clinical translation potential for AS management.
动脉粥样硬化（AS）是一种慢性炎症性疾病，是全球发病率和致残率的首要原因。在 AS 的发病机制中，炎症的主要过程高度涉及氧化应激的继发事件，但由于其非特异性作用、较差的生物安全性以及在斑块病变内的快速消除和尿液排泄以及较短的保留时间，目前临床上可用的抗氧化剂有限。在这项工作中，具有强大活性氧（ROS）清除能力的普鲁士蓝纳米酶被合理设计用于有效的 AS 纳米治疗。具体来说，获得的具有高热性能的纳米酶可以作为有效的声纳成像剂用于斑块检测。此外，这些具有多种酶活性的纳米酶可以降低细胞内 ROS 水平，发挥对 ROS 介导的巨噬细胞凋亡的细胞保护作用，并抑制泡沫细胞形成，显著抑制 AS 的发展。在细胞水平上通过转录组测序和载脂蛋白 E 小鼠主动脉窦切片的一系列免疫组织化学染色进一步验证了其潜在机制。最后，所设计的普鲁士蓝纳米酶的高生物相容性和生物安全性进一步保证了其在 AS 管理中的临床转化潜力。
