Near-Infrared Fluorescence Reporter Offering Real-Time Tracking and Differential Assessment of Ferroptosis Progressions In Vivo

Ferroptosis-mediated tumor intervention has recently been revealed to play multiple roles in biology. Real-time monitoring of ferroptosis progression is imperative for the immediate assessment of therapeutic responses and the adjustment of diagnostic regimens but challenging as well. Herein, we present an activatable probe (<b>DL-CL</b>) designed for NIR fluorescence visualization and differential assessment of tumor responses to ferroptosis. <b>DL-CL</b> features a hemicyanine skeleton that incorporates a chlorine atom and a methylparaben group, which are quenched by a dimethylthiocarbamate-responsive group. This design enables the activation of the probe's NIR signal specifically upon exposure to the ferroptosis-related biomarker hypochlorous acid (HOCl). The rapid, highly sensitive, and specific response characteristics of <b>DL-CL</b> facilitate the real-time tracking of HOCl dynamics across various ferroptosis-triggering pathways in cells. Furthermore, <b>DL-CL</b> demonstrates its superiority in tumor identification, providing effective assistance in image-guided tumor resection and ferroptosis-mediated tumor therapy evaluation. The results reveal that increased levels of HOCl were captured following the ferroptosis combination treatment, showing a positive correlation with tumor growth inhibition. We anticipate that <b>DL-CL</b> may serve as a promising imaging tool for predicting the cancer therapeutic efficacy.