Recyclable Endogenous H₂ S Activation of Self-Assembled Nanoprobe with Controllable Biodegradation for Synergistically Enhanced Colon Cancer-Specific Therapy.

Excessive production of hydrogen sulfide (H₂ S) plays a crucial role in the progress of colon cancer. Construction of tumor-specific H₂ S-activated smart nanoplatform with controllable biodegradation is of great significance for precise and sustainable treatment of colon cancer. Herein, an endogenous H₂ S triggered Co-doped polyoxometalate (POM-Co) cluster with self-adjustable size, controlled biodegradation, and sustainable cyclic depletion of H₂ S/glutathione (GSH) is designed for synergistic enhanced tumor-specific photothermal and chemodynamic therapy. The designed POM-Co nanocluster holds H₂ S 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 ¹ O₂ generation with GSH consumption, respectively. More importantly, the degraded POM-CoS is reactivated by endogenous H₂ S for recyclable and sustainable consumption of H₂ S 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.