Glutathione-activated near-infrared II fluorescent probe for lung metastatic diagnosis and intraoperative imaging of tumor

Accurate identification of intraoperative tumor lesions and effective treatment are crucial for improving surgical outcomes. Near-infrared (NIR) fluorescence imaging demonstrates advantages over traditional medical approaches in tumor interventions, garnering significant attention. However, clinically available imaging agents are generally limited by their "always on" characteristics, which can lead to non-specific imaging interference and "false-positive" results. In this context, we present a glutathione-activated NIR-II probe, LJ-GSH, designed for metastatic tumor imaging and specific imaging-guided tumor resection. LJ-GSH initially exhibits quenched fluorescence due to the weak electron-donating effect of the thiophenol moiety, which is recovered at 815/ 910 nm upon activation by the overexpressed levels of glutathione (GSH) in tumor cells and tissues, significantly enhancing the specificity of tumor imaging. This unique characteristic positions LJ-GSH as a reliable fluorescent sensor for monitoring GSH dynamics during physiological events. Notably, the probe's NIR-II emission feature markedly improves imaging contrast and resolution, facilitating real-time identification and imaging of lung metastatic lesions. With the aid of high-specific NIR-II imaging guidance, tumor tissues can be precisely resected, with the residual negative margin diameter reduced to approximately 0.2 mm. We envision that our tailored probe may offer an attractive option for clinical applications.