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.

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在各种癌细胞中过表达的γ-谷氨酰转肽酶（GGT）被认为是潜在的肿瘤生物标志物。因此，对于体内肿瘤成像和研究，迫切需要开发近红外（NIR）荧光GGT探针。然而，据我们所知，这样的GGT探针仍然很少。在这里，我们通过掺入γ来构建新的GGT可激活的NIR荧光探针HCAGlu-谷氨酰胺基作为识别单元直接进入NIR半花菁荧光团。HCAGlu对GGT表现出高度敏感和选择性的NIR荧光关闭响应。该探针已应用于细胞和组织切片成像，证明了HCAGlu能够在生物样品中原位区分不同GGT表达水平的能力。值得注意的是，已经在荷瘤小鼠中进行了体内荧光成像，证实了探针HCAGlu可以通过静脉内和肿瘤内注射在肿瘤部位迅速产生独特的荧光信号。HCAGlu的简单性和优异的性能使其在体内研究GGT的生理功能方面具有很高的潜力。

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