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

Area of Science:

• Biomedical Engineering
• Chemical Biology
• Molecular Imaging

Background:

• Fibroblast activation protein-alpha (FAPα) is a promising biomarker for cancer and other diseases.
• Current analytical tools for in vivo FAPα detection are limited.
• Developing sensitive and specific probes is crucial for FAPα-based diagnostics and therapeutics.

Purpose of the Study:

• To develop novel FAPα-activated fluorescent probes with enhanced properties.
• To evaluate the efficacy of these probes for in vivo FAPα imaging.
• To provide a powerful tool for FAPα-relevant physiological and pathological processes.

Main Methods:

• Design and synthesis of two novel FAPα-activated fluorescent probes, Sulfo-OHDF and Sulfo-FQCy7, based on hemicyanine and cyanine fluorophores.
• Introduction of a sulfonic acid group to improve water solubility.
• Evaluation of probe performance including signal-to-noise ratio, sensitivity, and biocompatibility.
• In vivo imaging experiments in cells, tumor tissues, and tumor-bearing mice.

Main Results:

• The novel probes exhibited significantly higher signal-to-noise ratios and sensitivity towards FAPα compared to control probes.
• Sulfo-OHDF demonstrated a 113.2-fold fluorescence enhancement and a limit of detection of 1.59 ng/mL.
• Successful detection of overexpressed FAPα in various biological models, including tumor tissues and mice.
• Sulfo-OHDF showed superior performance with near-infrared excitation/emission and improved biocompatibility.

Conclusions:

• Sulfo-OHDF and Sulfo-FQCy7 are effective FAPα-activated fluorescent probes with improved water solubility and sensitivity.
• Sulfo-OHDF is a highly sensitive and biocompatible probe suitable for in vivo FAPα imaging.
• These novel probes represent a powerful tool for advancing FAPα-based diagnostics and therapeutics, particularly in oncology.