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Real-time monitoring of γ-Glutamyltranspeptidase in living cells and in vivo by near-infrared fluorescent probe with large Stokes shift
Talanta ( IF 5.6 ) Pub Date : 2018-08-21 , DOI: 10.1016/j.talanta.2018.08.056
Feiyan Liu , Zhen Wang , Tianyu Zhu , Wenli Wang , Biao Nie , Jing Li , Yingjun Zhang , Jianguang Luo , Lingyi Kong

γ-Glutamyltranspeptidase (GGT) is a cell surface-bound enzyme that is closely implicated in various physiological disorders such as tumor. Thus, an efficient method for monitoring GGT is extremely important for biological studies and disease diagnosis. Herein, a near-infrared fluorescent probe (TMN-Glu) has been developed for turn-on trapping of GGT activity in vitro and in vivo based on conjugating a dicyanoisophorone derivative fluorophore with a GGT activatable γ-glutamyl amide moiety. Advantages of the probe include near-infrared emission (658 nm), with large Stokes shift (213 nm), high specificity, high sensitivity (LOD = 0.024 U/L), low cytotoxicity and high imaging resolution, allowing for the real-time imaging endogenous GGT in living cells. Probe TMN-Glu was highly feasible to report on the GGT levels in different types of cells. Notably, we also demonstrated its applicability in real-time visualizing endogenous GGT in tumor-bearing nude mice with low background interference. These results indicated that the probe held great promise for real-time sensing and tracking GGT in complex biological systems, which would be useful for basic researches and clinical diagnosis of GGT-related diseases.



中文翻译:

大斯托克斯频移的近红外荧光探针实时监测活细胞和体内γ-谷氨酰转肽酶

γ-谷氨酰转肽酶(GGT)是一种细胞表面结合酶,与多种生理疾病(例如肿瘤)密切相关。因此,监测GGT的有效方法对于生物学研究和疾病诊断极为重要。在本文中,基于将双氰基异佛尔酮衍生物荧光团与GGT可活化的γ-谷氨酰胺基团缀合,已经开发了用于在体外体内开启捕获GGT活性的近红外荧光探针(TMN-Glu)。该探针的优势包括近红外发射(658 nm),大斯托克斯位移(213 nm),高特异性,高灵敏度(LOD = 0.024 U / L),低细胞毒性和高成像分辨率,可实现实时成像活细胞中的内源性GGT。探测TMN-Glu在报告不同类型细胞中的GGT水平方面非常可行。值得注意的是,我们还证明了其在实时可视化具有低背景干扰的荷瘤裸鼠中内源GGT的适用性。这些结果表明,该探针对于复杂生物系统中GGT的实时传感和跟踪具有广阔的前景,将为GGT相关疾病的基础研究和临床诊断提供参考。

更新日期:2018-08-21
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