College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, China.
J Mater Chem B. 2019 Apr 21;7(15):2557-2564. doi: 10.1039/c9tb00079h. Epub 2019 Mar 20.
Hypoxic stress is a common concern in medicine and biology, which can induce the cellular injury and death by excess production of reactive oxygen species (ROS). Hypochlorous acid (HOCl), one of the ROS, plays a crucial role in the oxidative damage to tissue proteins in the pathogenesis of various diseases. Therefore, excess production of HOCl might be an important factor for the damage caused by hypoxic stress. However, most of the present methods cannot meet the demand of real-time detection on account of the labile and reactive chemical properties of HOCl. Herein, we designed a near-infrared fluorescent probe, Cy-HOCl, for the selective imaging of HOCl in cells and in vivo. Cy-HOCl includes two moieties: a 4-amino-3-nitrophenol group as the response unit and a near-infrared heptamethine cyanine fluorophore as the fluorescent modulator. Cy-HOCl exhibits excellent selectivity and sensitivity towards the detection of HOCl. The hypoxic response behavior of Cy-HOCl is evaluated in cells to clarify the relationship between HOCl and hypoxia. The probe is also applied to measure HOCl in ex vivo-dissected organs of an acute ischemia mouse model as well as for real-time monitoring the changes of HOCl in the hypoxic zebrafish model.
缺氧应激是医学和生物学中的一个常见问题,它会通过过量产生活性氧(ROS)引起细胞损伤和死亡。次氯酸(HOCl)是 ROS 之一,在各种疾病的发病机制中对组织蛋白的氧化损伤起着至关重要的作用。因此,HOCl 的过量产生可能是缺氧应激引起损伤的一个重要因素。然而,由于 HOCl 的化学性质不稳定且具有反应性,目前大多数方法都无法满足实时检测的需求。在这里,我们设计了一种近红外荧光探针 Cy-HOCl,用于细胞内和体内 HOCl 的选择性成像。Cy-HOCl 包括两个部分:一个 4-氨基-3-硝基苯酚基团作为响应单元和一个近红外庚甲川菁荧光团作为荧光调节剂。Cy-HOCl 对 HOCl 的检测表现出优异的选择性和灵敏度。在细胞中评估 Cy-HOCl 的缺氧反应行为,以阐明 HOCl 与缺氧之间的关系。该探针还用于测量急性缺血性小鼠模型离体器官中的 HOCl 以及实时监测缺氧斑马鱼模型中 HOCl 的变化。