State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.
Analyst. 2021 Mar 21;146(6):1865-1871. doi: 10.1039/d0an02232b. Epub 2021 Jan 22.
γ-Glutamyltranspeptidase (GGT) is an important aminopeptidase overexpressed in many malignant tumors, and accurate detection of its activity is useful for the diagnosis and treatment of tumors. Herein, we report a GGT-activatable ratiometric fluorescent probe (1) constructed by covalently linking an 'always-on' BODIPY fluorophore with a GGT-activatable near-infrared (NIR) fluorescent substrate. Upon interaction with GGT, the NIR fluorescence at 735 nm in probe 1 is significantly enhanced, while the fluorescence of BODIPY at 517 nm remains unchanged. Using BODIPY fluorescence as an internal standard, significantly enhanced ratiometric fluorescence between 735 nm and 517 nm could be achieved, allowing accurate detection of the activity of GGT in living subjects independent of probe concentration. We demonstrate that probe 1 is feasible for the evaluation of GGT levels in different tumor cells and differentiation of GGT-positive tumor cells from GGT-negative normal tissue cells. Moreover, probe 1 is further applied for the visualization of tumor via noninvasive ratiometric fluorescence imaging of GGT activity, which could facilitate the detection of GGT-positive tumor tissues and study of GGT-related pathological processes.
γ-谷氨酰转移酶（GGT）是许多恶性肿瘤中过度表达的一种重要的氨肽酶，其活性的准确检测对肿瘤的诊断和治疗很有帮助。在此，我们报告了一种通过共价连接“常开”BODIPY 荧光团和 GGT 激活的近红外（NIR）荧光底物构建的 GGT 激活比率荧光探针（1）。与 GGT 相互作用后，探针 1 中 735nm 处的近红外荧光显著增强，而 517nm 处的 BODIPY 荧光保持不变。利用 BODIPY 荧光作为内参，可实现 735nm 和 517nm 之间显著增强的比率荧光，可实现对活体内 GGT 活性的准确检测，而与探针浓度无关。我们证明了探针 1 可用于评估不同肿瘤细胞中的 GGT 水平，以及 GGT 阳性肿瘤细胞与 GGT 阴性正常组织细胞的分化。此外，探针 1 进一步用于通过非侵入性 GGT 活性比率荧光成像来可视化肿瘤，这有助于检测 GGT 阳性肿瘤组织和研究 GGT 相关的病理过程。
