Development of Enzyme-Activatable AIE Probes for Precision Theranostics

Abstract

Precision theranostics have become a vital component of the biomedical field, offering not only efficient disease targeting but also minimizing surgical wounds. High-specificity detection and treatment strategies help avoid harm to normal regions while focusing exclusively on diseased sites. Multifunctional fluorescent materials play a critical role in these strategies. However, traditional fluorescent probes are often prone to aggregation-caused quenching (ACQ). The discovery of aggregation-induced emission (AIE) in 2001 provided an effective solution to this problem. AIE luminogens (AIEgens) emit strongly in the aggregated state because of the restriction of intramolecular motion, making them well-suited for biomedical applications.

In this thesis, we developed enzyme-activatable AIE probes for the specific detection and treatment of cancer. A novel fibroblast activation protein-α (FAPα)-activatable fluorescent probe, OTBP-F, was designed with high specificity and excellent photoluminescent quantum yield. OTBP-F enabled real-time, fluorescence-guided imaging of orthotopic liver tumors in mice, facilitating precise intraoperative resection of both primary tumors and metastatic lesions.

Building upon this, we integrated antibody-directed enzyme prodrug therapy (ADEPT), a mutant β-galactosidase-based “bump-and-hole” strategy, and high-performance AIE materials for the precise diagnosis and treatment of bladder cancer. Through a bioorthogonal reaction between mutant β-galactosidase and 6-O-methylgalactose, the optical signal of the probe was selectively activated in bladder tumors. This approach allowed for early cancer diagnosis and guided tumor resection with improved accuracy, potentially enhancing therapeutic outcomes and reducing recurrence rates.

This research offers promising tools for precision cancer theranostics and contributes to the advancement of fluorescent probe development in biomedical science.

Date of Award	2025
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Jianwei SUN (Supervisor) & Benzhong TANG (Supervisor)