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Hypoxia imaging in living cells, tissues and zebrafish with a nitroreductase-specific fluorescent probe.
Analyst ( IF 3.6 ) Pub Date : 2020-06-23 , DOI: 10.1039/d0an00378f
Li Fan 1 , Qi Zan , Bo Lin , Xiaodong Wang , Xiaojuan Gong , Zhonghua Zhao , Shaomin Shuang , Chuan Dong , Man Shing Wong
Affiliation  

Hypoxia in solid tumors is directly linked to the elevated levels of endogenous nitroreductase (NTR). We present a novel fluorescent probe, namely NTNO, for nitroreductase-specific detection based on the NTR-catalyzed reduction of the nitro unit to an amine functionality, and demonstrated its application for hypoxia imaging. NTNO was designed by incorporating a nitro unit as the NTR response site into a benzothiazole derivative. Upon reacting with NTR in the presence of reduced nicotinamide adenine dinucleotide (NADH), the fluorescence of the probe was strongly and sensitively turned on, with a good linearity in the NTR concentration range of 0.5–8.0 μg mL−1 and a detection limit of 48 ng mL−1. Most notably, NTNO has been successfully used for imaging hypoxia levels in living cells, tumor tissues and zebrafish, making it of great potential to monitor NTR in biological systems.

中文翻译:

使用硝基还原酶特异性荧光探针在活细胞,组织和斑马鱼中进行低氧成像。

实体瘤中的缺氧与内源性硝基还原酶(NTR)水平升高直接相关。我们提出了一种新型的荧光探针,即NTNO,用于基于NTR催化的硝基单元还原成胺官能团的硝基还原酶特异性检测,并证明了其在低氧成像中的应用。通过将硝基单元作为NTR响应位点并入苯并噻唑衍生物来设计NTNO。在还原性烟酰胺腺嘌呤二核苷酸(NADH)存在下与NTR反应时,探针的荧光强烈而灵敏地开启,在NTR浓度范围为0.5–8.0μgmL -1时线性良好,检出限为48 ng毫升-1。最值得注意的是,NTNO 已成功地用于活细胞,肿瘤组织和斑马鱼中低氧水平的成像,使其具有监测生物系统中NTR的巨大潜力。
更新日期:2020-08-10
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