Depletion and Downregulation of Hydrogen Sulfide Using an Activatable Probe for Promoting Photothermal Therapy toward Colorectal Cancers
Xuemei Dong, Hongyu Wu, Ziwen Zhang, Jie Sun, Chengjun Dong, Lixin Sun, Rongchen Wang, Xianfeng Gu, Chunchang Zhao
Abstract
Since hydrogen sulfide (H 2 S) is an important endogenous gaseous mediator, therapeutic manipulation of H 2 S is promising for anticancer treatment. In this work, we develop a novel theranostic nanoplatform with H 2 S-specific and photocontrolled synergistic activation for imaging-guided H 2 S depletion and downregulation along with promoted photothermal therapy. Such a nanoplatform is fabricated by integration of a H 2 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 H 2 S-rich cancers, guiding further laser irradiation. Furthermore, prominent conversion of photoenergy into heat guarantees special container melting with controllable AOAA release for H 2 S-level downregulation. This smart regulation of the endogenous H 2 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 H 2 S-concerned cancer treatment with an optimized diagnostic and therapeutic effect.