Sichuan Key Laboratory of Medical Imaging, Affiliated Hospital of North Sichuan Medical College & Department of Chemistry, School of Preclinical Medicine, North Sichuan Medical College, Nanchong, 637000, China.
Sichuan Key Laboratory of Medical Imaging, Affiliated Hospital of North Sichuan Medical College & Department of Chemistry, School of Preclinical Medicine, North Sichuan Medical College, Nanchong, 637000, China.
Biosens Bioelectron. 2019 Oct 1;142:111497. doi: 10.1016/j.bios.2019.111497. Epub 2019 Jul 10.
Abnormal expression of γ-glutamyltranspeptidase (GGT) in living organisms is closely associated with tumorigenesis. However, few reported fluorescence probes can specifically respond to abnormal concentration of GGT. Here, by functionalizing triarylboron moiety with three GGT-specific substrate (GSH) units, a novel fluorescence probe, TAB-3-GSH, was developed for detecting GGT. The results showed that TAB-3-GSH selectively responds to abnormally high levels of GGT (100-1000 U/L) rather than to normal GGT levels (<100 U/L) with ratiometric readout, since the amide linkage can be further hydrolyzed under high GGT levels. TAB-3-GSH was also capable of differentiating GGT-overexpressing ovarian cancer cells from normal cells, because of an improvement in the probe's cell membrane permeability upon reaction with GGT. Moreover, the probe could achieve selective imaging of SKOV-3 tumor site in xenograft mice model. Thus, TAB-3-GSH is a promising probe for tumor targeting in vivo.
γ-谷氨酰转移酶（GGT）在生物体内的异常表达与肿瘤发生密切相关。然而，目前报道的荧光探针很少能够特异性地响应异常浓度的 GGT。在这里，通过将三芳基硼部分官能化三个 GGT 特异性底物（GSH）单元，开发了一种新型的荧光探针 TAB-3-GSH，用于检测 GGT。结果表明，TAB-3-GSH 选择性地响应异常高的 GGT 水平（100-1000 U/L），而不是正常的 GGT 水平（<100 U/L），具有比色读数，因为在高 GGT 水平下酰胺键可以进一步水解。TAB-3-GSH 还能够区分 GGT 过表达的卵巢癌细胞与正常细胞，因为与 GGT 反应后探针的细胞膜通透性得到改善。此外，该探针能够在异种移植小鼠模型中选择性地对 SKOV-3 肿瘤部位进行成像。因此，TAB-3-GSH 是一种有前途的用于体内肿瘤靶向的探针。
