Li Ruixi, Kassaye Habtamu, Pan Yanping, Shen Yuanzhi, Li Weiqing, Cheng Yuru, Guo Jingxuan, Xu Yue, Yin Hongping, Yuan Zhenwei
Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing City, China.
Biomater Sci. 2020 Nov 7;8(21):5994-6003. doi: 10.1039/d0bm01237h. Epub 2020 Sep 29.
Biothiols such as cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) play important roles in various physiological and pathological processes, and due to their similar structures and reaction activities, it is still challenging to simultaneously discriminate between GSH and Cys/Hcy in vivo. Hence, a novel fluorescent probe for simultaneously discriminating GSH and Cys/Hcy in biological samples is highly desirable. Herein, we presented two enhanced fluorescent probes (Cy1 and Cy2) with doubly-activated dual emission for sensitive and discriminative detection of Cys/Hcy and GSH. The probes were constructed with IR-780 and NBD linked via an ether bond, which responds to GSH with near infrared (NIR) emission at 810 nm (λ = 720 nm) and Cys/Hcy with visible green emission at 550 nm (λ = 470 nm). The probe Cy2 is operable in human serum samples, thus holding promise for its diagnosis-related application. Notably, the results of fluorescence microscopy imaging indicated that Cy2 is suitable for visualization of exogenous and endogenous biothiols in living cells. Furthermore, desirable results were obtained when the probe Cy2 was applied for bioimaging in tumor-bearing mice and acute liver injury (ALI) mice models, which revealed encouraging clinical values of this probe.
半胱氨酸（Cys）、同型半胱氨酸（Hcy）和谷胱甘肽（GSH）等生物硫醇在各种生理和病理过程中发挥着重要作用，由于它们结构和反应活性相似，在体内同时区分GSH与Cys/Hcy仍然具有挑战性。因此，非常需要一种能够同时区分生物样品中GSH和Cys/Hcy的新型荧光探针。在此，我们展示了两种具有双激活双发射的增强型荧光探针（Cy1和Cy2），用于灵敏且有区分性地检测Cys/Hcy和GSH。这些探针由通过醚键连接的IR-780和NBD构建而成，它对GSH的响应是在810 nm处产生近红外（NIR）发射（λ = 720 nm），对Cys/Hcy的响应是在550 nm处产生可见绿色发射（λ = 470 nm）。探针Cy2可在人血清样品中使用，因此在其诊断相关应用方面具有前景。值得注意的是，荧光显微镜成像结果表明Cy2适用于活细胞中外源和内源生物硫醇的可视化。此外，当探针Cy2应用于荷瘤小鼠和急性肝损伤（ALI）小鼠模型的生物成像时，获得了理想的结果，这揭示了该探针令人鼓舞的临床价值。
