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Activatable Near‐Infrared Probe for Fluorescence Imaging of γ‐Glutamyl Transpeptidase in Tumor Cells and In Vivo
Author(s) -
Luo Zhiliang,
Feng Liandong,
An Ruibing,
Duan Guanfu,
Yan Runqi,
Shi Hua,
He Jian,
Zhou Zhengyang,
Ji Changge,
Chen HongYuan,
Ye Deju
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201702210
Subject(s) - in vivo , fluorescence , fluorophore , chemistry , linker , fluorescence lifetime imaging microscopy , biophysics , enzyme , preclinical imaging , biomarker , biochemistry , cancer research , biology , physics , microbiology and biotechnology , quantum mechanics , computer science , operating system
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 −1 ) 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.