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In Vivo Visualization of γ-Glutamyl Transpeptidase Activity with an Activatable Self-Immobilizing Near-Infrared Probe
Analytical Chemistry ( IF 6.7 ) Pub Date : 2020-11-03 , DOI: 10.1021/acs.analchem.0c02954 Yuyao Li 1 , Chenghong Xue 1 , Zhijun Fang 1 , Weipan Xu 1 , Hexin Xie 1
Analytical Chemistry ( IF 6.7 ) Pub Date : 2020-11-03 , DOI: 10.1021/acs.analchem.0c02954 Yuyao Li 1 , Chenghong Xue 1 , Zhijun Fang 1 , Weipan Xu 1 , Hexin Xie 1
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γ-Glutamyl transpeptidase (GGT), a type of cell membrane-bound enzyme, is closely involved in a wide range of physiological and pathological processes, and a large number of fluorogenic probes have been developed to detect the activity of GGT. However, the use of these imaging reagents to visualize GGT activity in vivo is largely limited because of rapid diffusion and clearance of activated fluorophores. Herein, by merging quinone methide and a fluorogenic enzyme substrate, we report an activatable self-immobilizing near-infrared probe for the in vitro and in vivo imaging of GGT activity. This probe is initially fluorescently silent, but the selective activation by GGT is able to significantly increase its fluorescence intensity at 714 nm and covalently anchor activated fluorophores at the site of interest. We have shown that this probe induced a much stronger fluorescence on live GGT-overexpressing cells compared to regular fluorogenic probes and allowed wash-free and real-time imaging of enzyme activity. More importantly, the use of this probe in the imaging of GGT activity in U87MG tumor-bearing mice by i.v. administration indicates that this self-immobilizing reagent is capable of efficiently enhancing its retention at the detection target and thus leads to much improved detection sensitivity compared to regular fluorogenic probes. This study demonstrates the advantage of fluorogenic probes with activatable anchors in the noninvasive imaging of enzyme activity in highly dynamic in vivo systems.
中文翻译：
可激活的自固定近红外探针在体内可视化的γ-谷氨酰转肽酶活性。
γ-谷氨酰转肽酶（GGT）是一种细胞膜结合酶，与广泛的生理和病理过程密切相关，并且已开发出许多荧光探针来检测GGT的活性。然而，由于活化的荧光团的快速扩散和清除，使用这些成像试剂在体内可视化GGT活性受到很大限制。在这里，通过合并醌甲基化物和荧光酶底物，我们报告了GGT活性的体外和体内成像的可激活的自固定近红外探针。该探针最初是荧光沉默的，但是通过GGT进行的选择性激活能够显着增加其在714 nm处的荧光强度，并将共价激活的荧光团共价锚定在目标位点。我们已经显示，与常规的荧光探针相比，该探针在过表达GGT的活细胞上诱导了更强的荧光，并允许酶活性的免洗和实时成像。更重要的是，在通过静脉内给药在U87MG荷瘤小鼠的GGT活性成像中使用该探针表明，这种自固定试剂能够有效地增强其在检测靶标上的保留率，从而导致检测灵敏度大大提高。常规的荧光探针。这项研究证明了具有可激活锚的荧光探针在高动态体内系统中酶活性的非侵入性成像中的优势。
更新日期：2020-11-17
中文翻译：
可激活的自固定近红外探针在体内可视化的γ-谷氨酰转肽酶活性。
γ-谷氨酰转肽酶（GGT）是一种细胞膜结合酶，与广泛的生理和病理过程密切相关，并且已开发出许多荧光探针来检测GGT的活性。然而，由于活化的荧光团的快速扩散和清除，使用这些成像试剂在体内可视化GGT活性受到很大限制。在这里，通过合并醌甲基化物和荧光酶底物，我们报告了GGT活性的体外和体内成像的可激活的自固定近红外探针。该探针最初是荧光沉默的，但是通过GGT进行的选择性激活能够显着增加其在714 nm处的荧光强度，并将共价激活的荧光团共价锚定在目标位点。我们已经显示，与常规的荧光探针相比，该探针在过表达GGT的活细胞上诱导了更强的荧光，并允许酶活性的免洗和实时成像。更重要的是，在通过静脉内给药在U87MG荷瘤小鼠的GGT活性成像中使用该探针表明，这种自固定试剂能够有效地增强其在检测靶标上的保留率，从而导致检测灵敏度大大提高。常规的荧光探针。这项研究证明了具有可激活锚的荧光探针在高动态体内系统中酶活性的非侵入性成像中的优势。
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