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硝基还原酶激活的近红外荧光探针用于活体溃疡性结肠炎缺氧成像。

Activatable near-infrared fluorescent probe triggered by nitroreductase for in vivo ulcerative colitis hypoxia imaging.

机构信息

Institute of Optical Functional Materials for Biomedical Imaging, School of Chemistry and Pharmaceutical Engineering, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016, PR China.

Institute of Optical Functional Materials for Biomedical Imaging, School of Chemistry and Pharmaceutical Engineering, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016, PR China.

出版信息

Anal Chim Acta. 2022 Aug 15;1221:340107. doi: 10.1016/j.aca.2022.340107. Epub 2022 Jun 22.

Abstract

Ulcerative colitis is a prevalent inflammatory disease caused by the intestinal bacterial infection. And it is related to the hypoxic degrees in the colon microenvironment. Hypoxia, a condition of imbalance in O supply and consumption, is accompanied by the overexpressed level of nitroreductase (NTR). Therefore, the NTR detection has been widely applied for the diagnosis of hypoxia-related diseases. In this study, we developed a novel near-infrared fluorescent probe (IW-1) for NTR. Upon reaction with NTR, IW-1 exhibited a significant fluorescence off-on response at 740 nm with a low detection limit of 0.043 μg/mL. Confocal fluorescence imaging verified its ability to detect the overexpression of NTR in cancer cells. More significantly, IW-1 was applied for in vivo hypoxia imaging in tumors and dextran sulphate sodium (DSS)-induced ulcerative colitis mouse model. We expect that the probe may present a new tool for better understanding the biological functions of NTR as well as revealing essential information about hypoxia-related pathological processes, including cancer and ulcerative colitis.

摘要

溃疡性结肠炎是一种由肠道细菌感染引起的常见炎症性疾病。它与结肠微环境中的缺氧程度有关。缺氧是一种供氧和耗氧失衡的状态,伴随着硝基还原酶 (NTR) 的过度表达水平。因此,NTR 的检测已广泛应用于缺氧相关疾病的诊断。在这项研究中,我们开发了一种用于 NTR 的新型近红外荧光探针 (IW-1)。与 NTR 反应后,IW-1 在 740nm 处表现出显著的荧光开-关响应,检测限低至 0.043μg/mL。共聚焦荧光成像验证了其在癌细胞中检测 NTR 过表达的能力。更重要的是,IW-1 被应用于肿瘤内的体内缺氧成像和葡聚糖硫酸钠 (DSS) 诱导的溃疡性结肠炎小鼠模型。我们期望该探针可以为更好地理解 NTR 的生物学功能以及揭示包括癌症和溃疡性结肠炎在内的与缺氧相关的病理过程的重要信息提供一种新的工具。

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