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Abstract Gas‐mediated sonodynamic therapy (SDT) has the potential to become an effective strategy to improve the therapeutic outcome and survival rate of cancer patients. Herein, titanium sulfide nanosheets (TiS X NSs) are prepared as cascade bioreactors for sequential gas–sonodynamic cancer therapy. TiS X NSs themselves as hydrogen sulfide (H 2 S) donors can burst release H 2 S gas. Following H 2 S generation, TiS X NSs are gradually degraded to become S‐defective and partly oxidized into TiO X on their surface, which endows TiS X NSs with high sonodynamic properties under ultrasound (US) irradiation. In vitro and in vivo experiments show the excellent therapeutic effects of TiS X NSs. In detail, large amounts of H 2 S gas and reactive oxygen species (ROS) can simultaneously inhibit mitochondrial respiration and ATP synthesis, leading to cancer cell apoptosis. Of note, H 2 S gas also plays important roles in modulating and activating the immune system to effectively inhibit pulmonary metastasis. Finally, the metabolizable TiS X NSs are excreted out of the body without inducing any significant long‐term toxicity. Collectively, this work establishes a cascade bioreactor of TiS X NSs with satisfactory H 2 S release ability and excellent ROS generation properties under US irradiation for programmed gas–sonodynamic cancer therapy.
Li et al. (Fri,) studied this question.