硝基还原酶
自体荧光
荧光
癌细胞
荧光团
化学
生物物理学
原位
癌症
体外
癌症生物标志物
结直肠癌
共价键
双光子激发显微术
生物化学
癌症研究
生物
酶
遗传学
有机化学
物理
量子力学
作者
Chenfeng Xu,Zhongxi Huang,Jia Zhou,Wei Jiang,J Geng,Li Wang,Chibin Pu,Lin Li,Changmin Yu,Wei Huang
标识
DOI:10.1016/j.bios.2024.116768
摘要
Nitroreductase (NTR) is widely regarded as a biomarker whose enzymatic activity correlates with the degree of hypoxia in solid malignant tumors. Herein, we utilized 2-dimethylamino-7-hydroxynaphthalene as fluorophore linked diverse nitroaromatic groups to obtain four NTR-activatable two-photon fluorescent probes based on covalent assembly strategy. With the help of computer docking simulation and in vitro assay, the sulfonate-based probe XN3 was proved to be able to identify NTR activity with best performances in rapid response, outstanding specificity, and sensitivity in comparison with the other three probes. Furthermore, XN3 could detect the degree of hypoxia by monitoring NTR activity in kinds of cancer cells with remarkable signal-to-noise ratios. In cancer tissue sections of the breast and liver in mice, XN3 had the ability to differentiate between healthy and tumorous tissues, and possessed excellent fluorescence stability, high tissue penetration and low tissue autofluorescence. Finally, XN3 was successfully utilized for in situ visualizing NTR activities in human transverse colon and rectal cancer tissues, respectively. The findings suggested that XN3 could directly identify the boundary between cancer and normal tissues by monitoring NTR activities, which provides a new method for imaging diagnosis and intraoperative navigation of tumor tissue.
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