FAPα-Activated NIR-I Fluorescent Probe with Improved Water Solubility for Tumor Imaging

Fibroblast activation protein-α (FAPα), with restricted biological distribution and cleavage site specificity, is an attractive biomarker and target for diseases diagnosis and therapy, especially for cancers. However, effective analytical tools for in vivo FAPα detection are lacking. In this work, based on classic hemicyanine and cyanine fluorophores, we developed two novel FAPα-activated fluorescent probes, <b>Sulfo-OHDF</b> and <b>Sulfo-FQCy7</b>, with improved water solubility by introducing a sulfonic acid group into the fluorophore scaffold. Consequently, these probes exhibited much higher signal-to-noise ratios and sensitivity toward FAPα than the control probes. Among them, <b>Sulfo-OHDF</b>, featuring near infrared exciation/emssion, displayed superior fluorescence enhancement (113.2-fold), excellent sensitivity (limit of detection of 1.59 ng/mL) toward FAPα, and improved biocompatibility. Furthermore, using this probe, overexpressed FAPα in cells, tumor tissues, the wound-healing process, and tumor-bearing mice was successfully detected. Overall, our work may provide a powerful tool for in vivo imaging of FAPα-relevant physiological and pathological processes.