Chemosensor with Ultra-High Fluorescence Enhancement for Assisting in Diagnosis and Resection of Ovarian Cancer

Fluorescence imaging-guided diagnostics is one of the most promising approaches for facile detection of tumors in situ owing to its simple operation and non-invasiveness. As a crucial biomarker for primary ovarian cancers, beta-galactosidase (beta-gal) has been demonstrated to be the significant molecular target for visualization of ovarian tumors. Herein, a membrane-permeable fluorescent chemosensor (namely, LAN-beta gal) was synthesized for beta-gal-specific detection using the d-galactose residue as a specific recognition unit and LAN-OH (Phi(F) = 0.47) as a fluorophore. After beta-gal was digested, the fluorescence of the initially quenched LAN-beta gal (Phi(F) < 0.001) was enhanced by up to more than 2000-fold, which exceeded the fluorescence enhancement of other previously reported probes. We also demonstrated that the chemosensor LAN-beta gal could visualize endogenous beta-gal and distinguish ovarian cancer cells from normal ovarian cells.Further, the chemosensor LAN-beta gal was successfully applied to visualize the back tumor-bearing mouse model and peritoneal metastatic ovarian cancer model in vivo. More importantly, through in situ spraying, the proposed chemosensor was successfully employed to assist in the surgical resection of ovarian cancer tumors due to its high tumor-to-normal (T/N) tissue fluorescence ratio of 218. To the best of our knowledge, this is the highest T/N tissue fluorescence ratio ever reported. We believe that the LAN-beta gal chemosensor can be utilized as a new tool for the clinical diagnosis and treatment of ovarian cancer.