Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
Department of Chemistry, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
Anal Bioanal Chem. 2018 Oct;410(26):6771-6777. doi: 10.1007/s00216-018-1181-9. Epub 2018 Jun 16.
γ-Glutamyl transpeptidase (GGT), overexpressed in various cancer cells, has been perceived as a latent tumor biomarker. Thus, developing near-infrared (NIR) fluorescent GGT probes is highly desired for in vivo tumor imaging and studies. To our knowledge, however, such a GGT probe is still rare. Herein, we construct a new GGT-activatable NIR fluorescent probe HCAGlu by incorporating γ-glutamyl group as a recognition unit directly into a NIR hemicyanine fluorophore. HCAGlu exhibits a highly sensitive and selective NIR fluorescence off-on response to GGT. The probe has been applied to cell and histological section imaging, which demonstrates the ability of HCAGlu in distinguishing different GGT-expression levels in situ in biological samples. Notably, in vivo fluorescence imaging in tumor-bearing mice has been performed, verifying that probe HCAGlu can rapidly produce a distinct fluorescence signal in the tumor site via both intravenous and intratumoral injections. The simplicity and excellent performance of HCAGlu make it of high potential in studying the physiological function of GGT in vivo. Graphical abstract A near-infrared fluorescent probe for imaging γ-glutamyl transpeptidase in biological samples.
γ-谷氨酰转肽酶（GGT）在各种癌细胞中过表达，被认为是一种潜在的肿瘤生物标志物。因此，开发近红外（NIR）荧光 GGT 探针用于体内肿瘤成像和研究是非常需要的。然而，据我们所知，这样的 GGT 探针仍然很少。在此，我们通过将 γ-谷氨酰基直接作为识别单元整合到近红外半花菁荧光团中，构建了一种新型的 GGT 激活型 NIR 荧光探针 HCAGlu。HCAGlu 对 GGT 表现出高度敏感和选择性的 NIR 荧光关闭-开启响应。该探针已应用于细胞和组织切片成像，证明了 HCAGlu 在原位区分生物样品中不同 GGT 表达水平的能力。值得注意的是，在荷瘤小鼠中进行了体内荧光成像，验证了探针 HCAGlu 可以通过静脉内和肿瘤内注射快速在肿瘤部位产生明显的荧光信号。HCAGlu 的简单性和优异性能使其在研究 GGT 在体内的生理功能方面具有很高的潜力。
