PDF(Pubmed)
Abstract：
Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1β and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.
摘要：
急性肺损伤(ALI)是危重病人的一种危及生命的疾病,表现为肺部活性氧(ROS)和炎症因子水平过高。多项证据表明，具有多种催化能力的纳米酶在这种致命性肺损伤中起着至关重要的作用。目前,我们开发了一种新型的聚多巴胺（PDA）包被的二氧化铈（CeO2）纳米酶（Ce@P），可作为有效的ROS清除剂，用于清除细胞内ROS并抑制针对ALI的炎症反应。在这里，我们的目的是确定Ce@P结合NIR辐照可以进一步增强其清除ROS的能力。具体来说,NIR触发的Ce@P在脂多糖（LPS）诱导的巨噬细胞中通过降低细胞内ROS水平表现出最有效的抗氧化和抗炎行为，下调TNF-α水平，IL-1β和IL-6,上调抗氧化细胞因子(SOD-2)水平,诱导M2方向极化(CD206上调)，并增加HSP70的表达水平。此外,我们在LPS诱导的ALI大鼠模型中静脉注射Ce@P，发现它在注射后6小时内显著积累在肺组织中。还观察到Ce@P+NIR表现出减少肺部炎症的优良行为，缓解弥漫性肺泡损伤，以及促进肺组织修复。总而言之，它开发了使用Ce@P与NIR照射相结合的策略，用于ALI的协同增强治疗，这也可以作为ROS衍生疾病的临床治疗的有希望的治疗策略。
