Rational Design of Platinum–Bismuth Sulfide Schottky Heterostructure for Sonocatalysis‐Mediated Hydrogen Therapy

Conventional sonodynamic therapy is unavoidably limited by the tumor microenvironment, although many sonosensitizers have been developed to improve them to a certain extent. Given this, a concept of sonocatalytic hydrogen evolution is proposed, which is defined as an oxygen‐independent therapeutics. To demonstrate the feasibility of the concept, the narrow‐bandgap semiconductor bismuth sulfide (Bi2S3) is selected as the sonocatalyst and platinum (Pt) nanoparticles are grown in situ to optimize their catalytic performance. In this nanocatalytic system, the Pt nanoparticles help to capture sonoexcited electrons, whereas intratumoral overexpressed glutathione (GSH), as a natural hole sacrificial agent, can consume sonoexcited holes, which greatly improves the charge‐separation efficiency and promotes controllable and sustainable H2 generation. Even under hypoxic conditions, the Pt‐Bi2S3 nanoparticles can also produce sufficient H2 under ultrasound irradiation. Mechanistically, mitochondrial dysfunction caused by H2 and intratumoral redox homeostasis destruction by GSH depletion synergistically damage DNA to induce tumor cells apoptosis. At the same time, the Pt nanoparticles and holes can also trigger the decomposition of hydrogen peroxide into O2 to relieve tumor hypoxia, thus being synergistic with GSH depletion to reverse tumor immunosuppressive microenvironment. The proposed sonocatalysis‐mediated therapy will provide a new direction to realize facile and efficient cancer therapy. The concept of sonocatalytic hydrogen evolution is first proposed. The synthesized platinum–bismuth sulfide nanoparticles exhibit ultrasound‐catalyzed hydrogen production, glutathione oxidation, relieve hypoxia in vitro and in vivo, and effectively kill cancer cells by inhibiting cancer cell energy metabolism, increasing intratumoral reactive oxygen species levels, and inducing DNA damage.