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

Since hydrogen sulfide (H2 S) is an important endogenous gaseous mediator, therapeutic manipulation of H2 S is promising for anticancer treatment. In this work, we develop a novel theranostic nanoplatform with H2 S-specific and photocontrolled synergistic activation for imaging-guided H2 S depletion and downregulation along with promoted photothermal therapy. Such a nanoplatform is fabricated by integration of a H2 S-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 H2 S-rich cancers, guiding further laser irradiation. Furthermore, prominent conversion of photoenergy into heat guarantees special container melting with controllable AOAA release for H2 S-level downregulation. This smart regulation of the endogenous H2 S 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 H2 S-concerned cancer treatment with an optimized diagnostic and therapeutic effect.