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用于在活细胞和小鼠中成像内源性过氧亚硝酸盐的生物发光探针。

A Bioluminescent Probe for Imaging Endogenous Peroxynitrite in Living Cells and Mice.

机构信息

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Life Sciences , Hunan University , Changsha 410082 , China.

Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry , Xiangtan University , Xiangtan 411105 , P. R. China.

出版信息

Anal Chem. 2018 Mar 20;90(6):4167-4173. doi: 10.1021/acs.analchem.8b00198. Epub 2018 Feb 28.

Abstract

Peroxynitrite (ONOO), an extremely reactive nitrogen species (RNS), is implicated in diverse pathophysiological conditions, including cancer, neurodegenerative diseases, and inflammation. Sensing and imaging of ONOO in living systems remains challenging due to the high autofluorescence and the limited light penetration depth. In this work, we developed a bioluminescent probe BP-PN, based on luciferase-luciferin pairs and the ONOO-responded group α-ketoamide, for highly sensitive detection and imaging of endogenous ONOO in living cells and mice for the first time. Attributed to the BL without external excitation, the probe BP-PN exhibits a high signal-to-noise ratio with relatively low autofluorescence. Furthermore, we examine the application of the probe BP-PN using the mice model of inflammation, and BP-PN shows high sensitivity for imaging endogenous ONOO in inflamed mice. This newly developed bioluminescent probe would be a potentially useful tool for in vivo imaging of ONOO in wider physiological and pathological processes.

摘要

过氧亚硝酸盐(ONOO-)是一种反应性极强的氮自由基(RNS),与多种病理生理状况有关,包括癌症、神经退行性疾病和炎症。由于其自发荧光较高且光穿透深度有限,因此在活系统中对 ONOO-的感应和成像仍然具有挑战性。在这项工作中,我们首次基于荧光素酶-荧光素对和 ONOO-反应性的α-酮酰胺基团,开发了一种生物发光探针 BP-PN,用于活细胞和小鼠内源性 ONOO-的高灵敏度检测和成像。由于 BL 无需外部激发,探针 BP-PN 具有较高的信噪比和相对较低的自发荧光。此外,我们使用炎症小鼠模型来检验探针 BP-PN 的应用,结果表明 BP-PN 对成像炎症小鼠内源性 ONOO-具有很高的灵敏度。这种新开发的生物发光探针将成为更广泛生理和病理过程中体内成像 ONOO-的一种潜在有用工具。

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