LAUSR

Excessive production of hydrogen sulfide (H2S) plays a crucial role in the progress of colon cancer. Construction of tumor‐specific H2S‐activated smart nanoplatform with controllable biodegradation is of great significance for precise and sustainable treatment of colon cancer. Herein, an endogenous H2S triggered Co‐doped polyoxometalate (POM‐Co) cluster with self‐adjustable size, controlled biodegradation, and sustainable cyclic depletion of H2S/glutathione (GSH) is designed for synergistic enhanced tumor‐specific photothermal and chemodynamic therapy. The designed POM‐Co nanocluster holds H2S responsive “turn‐on” photothermal property in colon cancer via self‐assembling to form large‐sized POM‐CoS, enhancing the accumulation at tumor sites. Furthermore, the formed POM‐CoS can gradually biodegrade, resulting in release of Co2+ and Mo6+ for Co(II)‐catalyzed •OH production and Russell mechanism‐enabled 1O2 generation with GSH consumption, respectively. More importantly, the degraded POM‐CoS is reactivated by endogenous H2S for recyclable and sustainable consumption of H2S and GSH, resulting in tumor‐specific photothermal/chemodynamic continuous therapy. Therefore, this study provides an opportunity of designing tumor microenvironment‐driven nanoprobes with controllable biodegradation for precise and sustainable anti‐tumor therapy.