A thiol-triggered croconaine-chromene integration to induce ferroptosis and photothermal synergistic efficient tumor ablation.

Theranostic probes, combining diagnostic and treatment capabilities, have emerged as promising tools in tumor precision medicine. However, existing probes with constant fluorescence and photothermal activity can result in low signal-to-background ratios and phototoxicity. In this study, we introduced CM-Croc, a novel probe comprised of chromene and croconaine, selectively triggered by thiol. CM-Croc exhibited turn-on fluorescence and released croconaine for photothermal therapy. The croconaine moiety possesses high photothermal conversion efficiency up to 55%. Besides, it demonstrated potent activity against various cancer cell lines at low micromolar concentrations, including drug-resistant variants, through enhanced photothermal therapy combined with the ferroptosis effect. What's more, CM-Croc was proved to inhibit the activity of GPX4 to induce ferroptosis. Finally, CM-Croc was demonstrated to be the first croconaine-derived SOP, which targeted tumors and significantly inhibited tumor growth in vivo following intravenous administration with irradiation. This study showed CM-Croc's potential for enhancing tumor precision medicine.