Red-emitting fluorescent probes based on sulfur-substituted barbituric acid derivatives: synthesis, properties and biomedical applications

Abstract

Fluorescence bioimaging has emerged as a vital tool for tracking dynamic biochemical processes and monitoring disease biomarkers in vivo. This technique has demonstrated significant clinical and commercial potential in fluorescence-guided surgery (FGS) for tumor treatment, attributed to its real-time visualization capabilities and high biocompatibility. To achieve precise delineation of tumor boundaries and complete tumor resection, the rational design and selection of contrast agents are critical. Herein, we report a novel red-emitting fluorophore, TTS, based on thiobarbituric acid (TBA) derivatives and tetraphenylethylene. The design strategy, synthetic route, optical properties, and cytotoxicity of TTS are systematically described. Benefiting from its highly twisted molecular conformation and enhanced intramolecular charge transfer (ICT) effect, TTS exhibits superior aggregation-induced emission (AIE) characteristics with emission wavelengths extending into the NIR-I region (700–900 nm), as well as a reactive oxygen species (ROS)-generating capability. Systematic in vivo evaluations further demonstrate that TTS nanoparticles (NPs), which were formulated with DSPE-PEG2000 encapsulation, can accurately illuminate osteosarcoma tissues and effectively guide surgical resection through the enhanced permeability and retention (EPR) effect. This novel fluorophore not only boosts the development of AIE-based medical materials but also benefits intraoperative fluorescence imaging for clinical applications.