Biodegradable Bismuth‐Based Nano‐Heterojunction for Enhanced Sonodynamic Oncotherapy through Charge Separation Engineering

Sonodynamic therapy is a noninvasive treatment method that generates reactive oxygen species (ROS) triggered by ultrasound, to achieve oxidative damage to tumors. However, methods are required to improve the efficiency of ROS generation and achieve continuous oxidative damage. A ternary heterojunction sonosensitizer composed of Bi@BiO2−x@Bi2S3‐PEG (BOS) to achieve thermal injury‐assisted continuous sonodynamic therapy for tumors is prepared. The oxygen vacancy in BOS can capture hot electrons and promotes the separation of hot carriers on the bismuth surface. The local electric field induced by localized surface plasmon resonance also contributes to the rapid transfer of electrons. Therefore, BOS not only possesses the functions of each component but also exhibits higher catalytic activity to generate ROS. Meanwhile, BOS continuously consumes glutathione, which is conducive to its biodegradation and achieves continuous oxidative stress injury. In addition, the photothermal conversion of BOS under near‐infrared irradiation helps to achieve thermal tumor damage and further relieves tumor hypoxia, thus amplifying the sonodynamic therapeutic efficacy. This process not only provides a strategy for thermal damage to amplify the efficacy of sonodynamic therapy, but also expands the application of bismuth‐based heterojunction nanomaterials as sonosensitizers in sonodynamic therapy. Bismuth‐based ternary nano‐heterojunction semiconductor with biodegradable property and the characteristics of oxygen defects and the localized surface plasmon resonance are presented, which can enhance charge separation and regulate the generation of reactive oxygen species, thereby achieving the photothermal‐enhanced sonodynamic therapy of hypoxic tumors.