Intensive Care Unit, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China.
Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi, 530021, China.
J Nanobiotechnology. 2024 Jun 8;22(1):321. doi: 10.1186/s12951-024-02570-w.
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 (CeO) 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.
急性肺损伤(ALI)是危重病患者的一种危及生命的疾病,其特征是肺部活性氧(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,我们开发了一类新型的聚多巴胺(PDA)包覆的二氧化铈(CeO)纳米酶(Ce@P),它可以作为有效的 ROS 清除剂,清除细胞内的 ROS,并抑制对 ALI 的炎症反应。在此,我们旨在确定 Ce@P 与近红外(NIR)照射结合可以进一步增强其 ROS 清除能力。具体来说,NIR 触发的 Ce@P 通过降低细胞内 ROS 水平、下调 TNF-α、IL-1β 和 IL-6 的水平、上调抗氧化细胞因子(SOD-2)的水平、诱导 M2 定向极化(CD206 上调),并增加 HSP70 的表达水平,在脂多糖(LPS)诱导的巨噬细胞中表现出最强的抗氧化和抗炎作用。此外,我们在 LPS 诱导的 ALI 大鼠模型中进行了 Ce@P 的静脉(IV)注射,发现注射后 6 小时它在肺组织中大量积累。还观察到 Ce@P+NIR 表现出降低肺炎症、减轻弥漫性肺泡损伤以及促进肺组织修复的优越行为。总之,该研究提出了一种使用 Ce@P 结合 NIR 照射的协同增强治疗 ALI 的策略,可为 ROS 相关疾病的临床治疗提供一种有前途的治疗策略。
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