Development of a xanthene-based NIR fluorescent probe for accurate and sensitive detection of γ-glutamyl transpeptidase in cancer diagnosis and treatment†

γ-Glutamyl transpeptidase (GGT) regulates glutathione (GSH), essential for cell functions and linked to cancer. High GGT levels in tumors make it a valuable cancer biomarker. Current GGT detection methods often lack sensitivity and specificity. To address this, we developed XM-Glu, a new near-infrared (NIR) fluorescent probe. XM-Glu features a xanthene-based structure with a hydroxy xanthene fluorophore and a malononitrile group for NIR emission and reduced background noise. It has a self-immolating linker masked with glutamate acid, which activates fluorescence when GGT is present. XM-Glu can detect GGT in the range of 1.0 to 20 mU with a low detection limit of 0.067 mU mL⁻¹. It showed high specificity and minimal interference in cellular assays. In mice, XM-Glu effectively detected GGT in tumor, liver, and kidney tissues. Its NIR properties provide real-time insights into GGT activity, improving cancer diagnosis and monitoring. This new technology enhances cancer research and helps better understand GGT's role in cancer progression.