Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen 518060, China.
Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China.
Anal Chem. 2021 Dec 28;93(51):17103-17109. doi: 10.1021/acs.analchem.1c04504. Epub 2021 Dec 14.
Visualization of glutathione (GSH) enables us to understand GSH-related pathophysiological processes in living subjects. Currently, visualization methods of GSH are based on visible or first near-infrared (NIR-I) window fluorescence (FL) probes, which possess limitations due to their low tissue penetration depth and strong tissue autofluorescence. Herein, we developed a GSH-activatable second near-infrared (NIR-II) window FL probe (denoted as LET-7) for highly sensitive and selective visualization of GSH . LET-7, composed of an anionic polymethylcyanide skeleton linked with a FL quenching group of 3,5-bis(trifluoromethyl)benzenethiol, can be specifically activated by GSH, thus triggering a significant NIR-II FL emission enhancement with excellent photostability, which enables us to efficiently distinguish GSH from closely related low-molecular-weight biothiols. The limit of detection of LET-7 for GSH was determined to be as low as 85 nM. Most intriguingly, the studies demonstrated that LET-7 showed high sensitivity and good selectivity toward GSH. Therefore, our study provides a solution to design activatable NIR-II FL probes for imaging of GSH and other disease-related biomarkers.
可视化谷胱甘肽(GSH)使我们能够了解活体内与 GSH 相关的病理生理过程。目前,GSH 的可视化方法基于可见或近红外一区(NIR-I)荧光(FL)探针,由于其组织穿透深度低和强组织自发荧光,存在局限性。在此,我们开发了一种 GSH 激活的近红外二区(NIR-II)FL 探针(表示为 LET-7),用于高度灵敏和选择性地可视化 GSH。LET-7 由阴离子聚甲基氰骨架与 3,5-双(三氟甲基)苯硫醇的 FL 猝灭基团相连,可被 GSH 特异性激活,从而触发优异的光稳定性的显著 NIR-II FL 发射增强,使我们能够有效地将 GSH 与密切相关的低分子量生物硫醇区分开来。LET-7 对 GSH 的检测限低至 85 nM。最有趣的是,研究表明 LET-7 对 GSH 具有高灵敏度和良好的选择性。因此,我们的研究为设计用于 GSH 及其他与疾病相关生物标志物成像的激活型 NIR-II FL 探针提供了一种解决方案。