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 (DL-CL) designed for NIR fluorescence visualization and differential assessment of tumor responses to ferroptosis. DL-CL 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 DL-CL facilitate the real-time tracking of HOCl dynamics across various ferroptosis-triggering pathways in cells. Furthermore, DL-CL 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 DL-CL may serve as a promising imaging tool for predicting the cancer therapeutic efficacy.