Rational Design of Platinum-Bismuth Sulfide Schottky Heterostructure for Sonocatalysis-Mediated Hydrogen Therapy.

Conventional sonodynamic therapy (SDT) is unavoidably limited by the tumor microenvironment although many sonosensitizers have been developed to improve them to a certain extent. Given this, we propose a concept of sonocatalytic hydrogen evolution and define it as an oxygen-independent therapeutics. To demonstrate the feasibility of the concept, narrow-bandgap semiconductor bismuth sulfide (Bi 2 S 3 ) are selected as sonocatalysts and platinum (Pt) nanoparticles are grown in situ to optimize their catalytic performance. In this nanocatalytic system, Pt nanoparticles help to capture sono-excited electrons, whereas intratumoral overexpressed glutathione (GSH) as natural hole sacrificial agents can consume sono-excited holes, which greatly improves charge separation efficiency and promote the controllable and sustainable H 2 generation. Even under hypoxic conditions, the Pt-Bi 2 S 3 nanoparticles can also produce sufficient H 2 under US irradiation. Mechanistically, mitochondrial dysfunction caused by H 2 and intratumoral redox homeostasis destruction by GSH depletion synergistically damage DNA to induce tumor cells apoptosis. At the same time, Pt nanoparticles and holes can also trigger the decomposition of hydrogen peroxide into O 2 to relieve tumor hypoxia, thus 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. This article is protected by copyright. All rights reserved.