Luo Zhiliang, Feng Liandong, An Ruibing, Duan Guanfu, Yan Runqi, Shi Hua, He Jian, Zhou Zhengyang, Ji Changge, Chen Hong-Yuan, Ye Deju
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.
Shanghai Engineering Research Center for Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, P. R. China.
Chemistry. 2017 Oct 20;23(59):14778-14785. doi: 10.1002/chem.201702210. Epub 2017 Aug 18.
γ-Glutamyl transpeptidase (GGT) is a cell-membrane-bound enzyme that is involved in various physiological and pathological processes and is regarded as a potential biomarker for many malignant tumors, precise detection of which is useful for early cancer diagnosis. Herein, a new GGT-activatable near-infrared (NIR) fluorescence imaging probe (GANP) by linking of a GGT-recognitive substrate γ-glutamate (γ-Glu) and a NIR merocyanine fluorophore (mCy-Cl) with a self-immolative linker p-aminobenzyl alcohol (PABA) is reported. GANP was stable under physiological conditions, but could be efficiently activated by GGT to generate ≈100-fold enhanced fluorescence, enabling high sensitivity (detection limit of ≈3.6 mU L ) and specificity for the real-time imaging of GGT activity as well as rapid evaluation of the inhibition efficacy of GGT inhibitors in living tumor cells. Notably, the deep tissue penetration ability of NIR fluorescence could further allow GANP to image GGT in frozen tumor tissue slices with large penetration depth (>100 μm) and in xenograft tumors in living mice. This GGT activatable NIR fluorescence imaging probe could facilitate the study and diagnosis of other GGT-correlated diseases in vivo.
γ-谷氨酰转肽酶（GGT）是一种细胞膜结合酶，参与多种生理和病理过程，被视为多种恶性肿瘤的潜在生物标志物，对其进行精确检测有助于癌症早期诊断。在此，报道了一种新型的GGT可激活近红外（NIR）荧光成像探针（GANP），它通过将GGT识别底物γ-谷氨酸（γ-Glu）和近红外部花青荧光团（mCy-Cl）与自牺牲连接子对氨基苄醇（PABA）相连而成。GANP在生理条件下稳定，但可被GGT有效激活，产生约100倍增强的荧光，实现高灵敏度（检测限约为3.6 mU L）以及对GGT活性实时成像的特异性，还能快速评估GGT抑制剂在活肿瘤细胞中的抑制效果。值得注意的是，近红外荧光的深部组织穿透能力可进一步使GANP在大穿透深度（>100 μm）的冷冻肿瘤组织切片以及活体小鼠的异种移植肿瘤中对GGT进行成像。这种GGT可激活近红外荧光成像探针有助于体内其他与GGT相关疾病的研究和诊断。
