Depletion and Downregulation of Hydrogen Sulfide Using an Activatable Probe for Promoting Photothermal Therapy toward Colorectal Cancers

Since hydrogen sulfide (H₂S) is an important endogenous gaseous mediator, therapeutic manipulation of H₂S is promising for anticancer treatment. In this work, we develop a novel theranostic nanoplatform with H₂S-specific and photocontrolled synergistic activation for imaging-guided H₂S depletion and downregulation along with promoted photothermal therapy. Such a nanoplatform is fabricated by integration of a H₂S-responsive molecule probe that can generate a cystathionine-β-synthase (CBS) inhibitor AOAA and a photothermal transducer into an NIR-light-responsive container. Our nanoplatform can turn on NIR fluorescence specifically in H₂S-rich cancers, guiding further laser irradiation. Furthermore, prominent conversion of photoenergy into heat guarantees special container melting with controllable AOAA release for H₂S-level downregulation. This smart regulation of the endogenous H₂S level amplifies the PTT therapeutic effect, successfully suppressing colorectal tumor in living mice under NIR fluorescence imaging guidance. Thus, we believe that this nanoplatform may provide a powerful tool toward H₂S-concerned cancer treatment with an optimized diagnostic and therapeutic effect.