γ-谷氨酰转移酶近红外比率型荧光探针的设计与成像

Design and real-time biologic imaging of an NIR ratiometric fluorescent probe forγ-glutamyltransferase activity

γ-谷氨酰转肽酶(GGT)在诸多肿瘤组织中高表达,是一种重要的肿瘤标志物,对其活性的准确检测有助于相关疾病的早期诊断与治疗.本文将谷胱甘肽(GSH)共价修饰于七甲川花菁染料上作为GGT的酶切位点,研制了一例可用于GGT活性检测的近红外比率型荧光探针(Cy-GGT).该探针具有良好的水溶性,向其溶液中加入GGT,荧光发射波长由808 nm蓝移至616 nm(蓝移192 nm).较大的发射位移可避免两个信号之间的串扰,提高检测的准确性.实验表明,探针Cy-GGT可特异性检测GGT活性,检测限为0.02 mU/mL,并可用于活细胞和动物体中GGT的活性检测和荧光成像,能够区分肿瘤细胞与正常细胞,有望在相关疾病的早期诊断与治疗中发挥积极作用.

γ-Glutamyltranspeptidase(GGT)is considered as an important tumor marker,which is highly expressed in many human tumor tissues.Accurate detection of its activity is helpful for the early diagnosis and treatment of related diseases.In this work,a novel NIR ratiometric fluorescent probe(Cy-GGT)for GGT activity determination was developed by the judicious introduction of GSH,covalently bound to cyanine dye with a restriction site for GGT specifically.Upon the treatment with GGT in aqueous medium,by virtue of the excellent water solubility of Cy-GGT,the emission wavelength of Cy-GGT shifted from 808 to 616 nm,giving rise to an impressive emission displacement as far as 192 nm.The larger distance between the emission peaks can avoid the crosstalk between the two signals and improve the accuracy of detection.Cy-GGT shows a high selectivity for GGT activity with an LOD of 0.02 mU/mL.The ratiometric fluorescent probe was also workable for GGT activity determination and fluorescent imaging at cellular and in vivo levels,capable of distinguishing tumor cells from normal cells effectively.Encouraged by these pleasant performances,the application on early diagnosis and treatment of some certain cancers is expected and underway.