期刊
ANALYTICAL CHEMISTRY
卷 93, 期 20, 页码 7523-7531出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.1c01178
关键词
-
资金
- Global Research Laboratory Program - Ministry of Science, ICT, and Future Planning [NRF-2014K1A1A2064569]
- Basic Science Research Program - Ministry of Education [NRF-2019R1A2C2085438]
- Technology Development Program - Ministry of SMEs and Startups (MSS), Korea [S2632282]
- Korea Technology & Information Promotion Agency for SMEs (TIPA) [S2632282] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
A fluorescent NQO1 probe has been developed for practical ratiometric imaging in cells and tissues. The enzyme activity levels vary significantly in different organ tissues, with a markedly high level observed in xenograft tumor tissue compared to normal tissue, indicating potential for cancer diagnosis and enzyme-associated biology research.
NAD(P)H quinone oxidoreductase-1 (NQO1), a protective enzyme against cellular oxidative stress, is expressed abnormally high in solid tumors and thus recognized as a cancer biomarker. To develop a fluorescent NQO1 probe with practicality, we investigated benzo-rosol fluorophores linked with a known self-immolative quinone substrate. Four probe candidates exhibited ratiometric sensing behavior toward the enzyme, satisfying our orbital mismatch stratagem proposed before, under dual-excitation and dual-emission conditions that alleviate the spectral overlap issue commonly observed with the ratiometric probes based on intramolecular charge-transfer change. Among the candidates, two ester-linked compounds exhibited hydrolytic instability to water or an esterase, discouraging us to develop such ester-linked probes. One ether-linked, hydrolytically stable probe provided brighter cellular fluorescence than the other and thus was applied to ratiometric imaging of NQO1 in cells and tissues. We found that the enzyme activity levels are much different in organ tissues: stomach (56), kidney (22), colon (9.8), testis (7.8), bladder (5.6), lung (1.2), and muscle (1.0). Furthermore, a markedly high enzyme level (14.6-fold) was observed in a xenograft tumor tissue compared with that in a normal tissue, which suggests that such an NQO1 probe is promising for cancer diagnosis and for studying the enzyme-associated biology.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据