A mitochondrial-targeting near-infrared fluorescent probe for bioimaging and evaluating endogenous superoxide anion changes during ischemia/reperfusion injury
A mitochondrial-targeting near-infrared fluorescent probe for bioimaging and evaluating endogenous superoxide anion changes during ischemia/reperfusion injury
复制标题
一种靶向线粒体的近红外荧光探针，用于生物成像和评估缺血/再灌注损伤期间内源性超氧阴离子的变化。
DOI：
10.1016/j.biomaterials.2017.11.039
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发表时间：
2018-02-01
期刊：
影响因子：
14
通讯作者：
Chen, Lingxin
中科院分区：
文献类型：
--
作者：
Han, Xiaoyue;Wang, Rui;Chen, Lingxin
缺血/再灌注（I/R）过程中线粒体内超氧阴离子（O2-）的大量释放会引起线粒体膜电位极性丧失、次级细胞钙超载、细胞凋亡等一系列氧化损伤。为了监测I/R过程中O-2（center dot-）水平的变化，以及评价O-2（center dot-）浓度与细胞凋亡程度的关系，我们提出了一种比率型近红外线粒体靶向荧光探针Mito-Cy-Tfs，用于检测细胞内和体内O-2（center dot-）水平的变化。探针Mito-Cy-Tfs由三个部分组成：近红外七甲川菁作为荧光信号转导子，三氟甲磺酰胺作为荧光调节子，亲脂性三苯基膦阳离子作为线粒体导向子。该探针能很好地定位于线粒体内，选择性、灵敏地响应内源性O-2（中心点-）浓度的变化。该探针已成功地用于四种细胞I/R模型（葡萄糖剥夺/再灌注、血清剥夺/再灌注、氧剥夺/再灌注和葡萄糖-血清-氧剥夺/再灌注）中内源性O-2（中心点-）波动的成像。该探针还表现出较深的组织穿透性，用于I/R小鼠模型肝脏中O-2（中心点-）浓度的实时成像。我们证实了采用缺血预处理（IPC）和后处理（IPTC）对肝脏I/R损伤具有保护作用。该探头可准确地指示和评价I/R、IPC和IPTC过程中O-2（中心点-）水平与器官损伤程度的相互关系。上述应用使我们的新探针成为临床手术评估的潜在候选者。(C)2017爱思唯尔有限公司版权所有
The outburst of superoxide anion (O-2(center dot-)) in mitochondrial during ischemia/reperfusion (I/R) process will cause a series of oxidative damage including polarity loss of mitochondrial membrane potential, overload of secondary cellular calcium, and cascade apoptosis. To monitor the O-2(center dot-) level fluctuations as well as to evaluate the relationship between O-2(center dot-) concentration and the degree of cell apoptosis during I/R process, we propose a ratiometric near-infrared mitochondrial targeting fluorescent probe Mito-Cy-Tfs for the detection of level changes of O-2(center dot-) in cells and in vivo. The probe Mito-Cy-Tfs is composed of three moieties: near-infrared heptamethine cyanine as fluorescence signal transducer, trifluoromethanesulfonamide as fluorescence modulator, and lipophilic triphenylphosphonium cation as mitochondrial guider. The probe can well locate in mitochondria and respond the concentration changes of endogenous O-2(center dot-) selectively and sensitively. The probe has been successfully utilized to image the endogenous O-2(center dot-) fluctuations in four kinds of cell I/R models (glucose deprivation/reperfusion, serum deprivation/reperfusion, oxygen deprivation/reperfusion and glucose-serum-oxygen deprivation/reperfusion). The probe also exhibits deep tissue penetration for real-time imaging of O-2(center dot-) concentration in liver of I/R mice model. We confirm that the adoption of ischemic preconditioning (IPC) and postconditioning (IPTC) can protect liver from I/R injury. The probe can be employed to accurately indicate and evaluate the mutual relationship between the levels of O-2(center dot-) and the degrees of organ damage during I/R, IPC and IPTC processes. The above applications make our new probe a potential candidate for the clinical surgery assessment. (C) 2017 Elsevier Ltd. All rights reserved.