硝基还原酶
化学
体内
嘧啶
荧光
癌细胞
生物物理学
双光子激发显微术
生物化学
酶
癌症
生物
遗传学
量子力学
物理
生物技术
作者
J. Zhou,S. S. Fang,Duoteng Zhang,Yunwei Qu,Lan Wang,Sijun Pan,Lin Li,Jie Li,Wei Du,Qiong Wu
标识
DOI:10.1016/j.snb.2023.134015
摘要
Nitroreductase (NTR) is an overexpressed enzyme in hypoxic tumor microenvironment that can be a specific recognition site for tumor diagnosis in clinical trials. Therefore, the development of probs for NTR activity with precision and instantaneity is significant. In this work, a NTR probe (ZJ) was constructed on the structure of pyrimidine derivatives with 4-animobenzyl carbamate groups. ZJ exhibited a responsive “turn-on” two-photon excited fluorescence by NTR recognition in cells and in vivo. The 4-nitrobenzyl carbamate groups in ZJ could be reduced by NTR to 4-animobenzyl carbamate groups in the presence of reduced nicotinamide adenine dinucleotide (NADH). Attributed to its self-immolation property, 4-animobenzyl carbamate would release to generate primary amine on pyrimidine, accompanied by fluorescence signal recovery of ZJ. Such responsive fluorescence turn-on process accomplished as fast as within 20 mins. The favorable stability and specificity of ZJ on NTR activity sensing was further illustrated according to the negligible interference by biological factors and the distinguishing on different NTR types. ZJ successfully visualized the distribution of over-expressed NTR in hypoxic cancer cells and in zebrafish using two-photon fluorescence microscopy, which demonstrated the potential application in studying the relationship between tumor hypoxic microenvironment and cancer.
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