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

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