A Solid-State Near-Infrared Fluorescent Probe by a Synergistic Extended Conjugated System for Detecting Cys with Long-Term Imaging in Orthotopic Bladder Cancer

Bladder cancer (BC) is a highly prevalent malignant tumor of the urinary system with high recurrence and mortality rates. Currently, urine cytology and imaging techniques exhibit insufficient sensitivity for low-grade early tumors, while clinically used surgery navigation agents suffer from short tumor retention time. To address these limitations, this study develops a solid-state fluorescent probe, HPQ-TH-BI-Cys, enabling a specific response to cysteine (Cys) for precise identification and long-term imaging of bladder cancer. The solid-state fluorophore (HPQ-TH-BI) is designed by incorporating thiophene and benzoindole moieties into the HPQ core, forming a synergistic extended π-conjugated system that shifts the emission wavelength to the near-infrared region (750 nm). Using an acrylate group as the recognition unit, the probe (HPQ-TH-BI-Cys) undergoes specific cleavage in the presence of Cys, releasing HPQ-TH-BI, which is solid-state in water and shows long-term fluorescence. The cell experiments demonstrate that HPQ-TH-BI-Cys monitors dynamic changes in Cys concentrations and accurately distinguishes between normal cells and cancer cells. In vivo imaging experiments further reveal that the probe not only performs well in a mouse subcutaneous tumor model but also exhibits outstanding performance in an orthotopic bladder cancer model. Compared with the clinically used indocyanine green (ICG), HPQ-TH-BI-Cys provides higher accuracy for tumor imaging and longer imaging time, which offers a promising imaging tool for precise diagnosis and surgical navigation of bladder cancer.