Debut of Enzyme-Responsive Anionic Cyanine for Overlap-Free NIR-II-to-I Dual-Channel Tumour Imaging

Bridging the disparity between traditional surgical resection imaging and ex vivo histopathology, fluorescence imaging is considered a promising tool in disease diagnosis and imaging navigation. Nevertheless, its usefulness is undermined by the variability of single-wavelength fluorescence signals and limited penetration of NIR-I (650-900 nm) bioimaging. In this work, we present a novel NIR-II ratiometric fluorescent probe (CFC-GSH) with gamma-glutamyl transpeptidase (GGT) sensitivity for multifunctional bioimaging. This probe leverages a GSH-capped anionic cyanine, with advantages of high brightness, excellent photostability, high specificity and favourable biocompatibility. CFC-GSH exhibits an intrinsically stable NIR-II signal prior to triggering, which can be utilized for in vivo systemic circulation vessel outlining and microvascular imaging. At the tumour site with GGT over expression, an intramolecular S,N-rearrangement would initiate the conversion of sulphur-substituted cyanine to amino-substituted cyanine, resulting in a significant emission shift of 270 nm. Using the dual-channel signal changes, CFC-GSH effectively differentiates between subcutaneous hepatocellular carcinoma (HCC) and normal tissue and precisely localizes metastatic HCC tumours in the abdominal cavity. These results reveal that CFC-GSH exhibits promising potential as a multiprospective candidate tool for fluorescence screening and diagnostic imaging in various biological scenarios.