超声动力疗法（SDT）是一种利用超声触发的关键声敏剂进行物理疗法，以实现有效的非侵入性肿瘤治疗。然而，传统无机声敏剂的超声动力效能不足和反应活性低下一直阻碍着其实际应用。在这里，我们设计了一种铂-氧化锌（Pt-ZnO）声敏剂，通过其固有的禁带结构和双重纳米酶活性显著增强SDT的效能。Pt-ZnO具有窄禁带（2.89 eV）和适量的氧缺陷，促进电子和空穴分离效率以及在超声辐照下产生活性氧自由基（ROS）的生成。同时，Pt-ZnO表现出类过氧化物酶和过氧化酶活性，有效将内源性H2O2催化成大量的O2和有毒羟自由基（•OH），从而实现对SDT和催化治疗的高效增强。此外，Pt-ZnO具有显著的谷胱甘肽消耗性能，进一步增强氧化应激。最终，Pt-ZnO实现了三重ROS放大效应，单态氧（1O2）和•OH的产量分别达到859.1%和614.4%，诱导出具有显著肿瘤抑制率98.1%的高效超声催化疗法。本研究扩展了ZnO半导体异质结在纳米医学领域的应用，并且Pt-ZnO简单而高效的设计为声敏剂的开发提供了一种策略。 研究意义声明：我们构建了一种铂-氧化锌（Pt-ZnO）异质结声敏剂，具有双重纳米酶活性，实现了三重ROS放大效应，从而实现高效协同声敏催化疗法。Pt-ZnO具有固有的窄禁带和丰富的氧缺陷，因此具有高效的声敏剂性能。它还具有类过氧化物酶和过氧化酶活性，有效将内源性H2O2催化成大量的O2和有毒羟自由基，从而增强了SDT和催化治疗。此外，它突出的谷胱甘肽消耗性能进一步增强了氧化应激。单态氧和羟自由基的产量分别达到了859.1%和614.4%，诱导出具有显著肿瘤抑制率98.1%的高效声敏催化疗法。版权所有 © 2023. 由 Elsevier Ltd. 发布。

Sonodynamic therapy (SDT) is a physical therapy that utilizes critical sonosensitizers triggered by ultrasound to achieve an effective non-invasive tumor treatment. However, the inadequate sonodynamic efficacy and low responsive activities of traditional inorganic sonosensitizers have hindered its practical application. Here, we rationally design a platinum-zinc oxide (Pt-ZnO) sonosensitizer to significantly enhance the efficacy of SDT through its inherent bandgap structure and dual-nanozyme activities. The Pt-ZnO possesses a narrow bandgap (2.89 eV) and an appropriate amount of oxygen defects, which promote the efficiency of electrons and holes separation and the generation of reactive oxygen species (ROS) under US irradiation. Simultaneously, the Pt-ZnO exhibits both catalase-like and peroxidase-like activities, which effectively catalyze endogenous H2O2 into a large number of O2 and toxic hydroxyl radicals (•OH), thus achieving an efficient enhancement of SDT and catalytic therapy. Moreover, the Pt-ZnO has significant glutathione consumption performance, further amplifying the oxidative stress. Ultimately, the Pt-ZnO achieves a triple ROS amplification effect, with the yields of singlet oxygen (1O2) and •OH reaching 859.1% and 614.4%, respectively, inducing a highly effective sono-catalytic therapy with a remarkable tumor inhibition rate of 98.1%. This study expands the application of ZnO semiconductor heterojunctions in the nanomedicine area, and the simple yet efficient design of the Pt-ZnO provides a strategy for the development of sonosensitizers. STATEMENT OF SIGNIFICANCE: : A platinum-zinc oxide (Pt-ZnO) heterojunction sonosensitizer is constructed with dual-nanozyme activities and achieves a triple ROS amplification effect, leading to an efficient synergistic sono-catalytic therapy. The Pt-ZnO owns an inherent narrow bandgap and abundant oxygen defects, thus exhibiting an efficient sonosensitizer performance. It also possesses both catalase-like and peroxidase-like activities, which effectively catalyze the endogenous H2O2 into a large quantity of O2 and toxic hydroxyl radicals, thereby enhancing the SDT and catalytic therapy. Furthermore, its prominent glutathione consumption performance further amplifies oxidative stress. The yields of singlet oxygen and hydroxyl radicals reach up to 859.1% and 614.4%, respectively, inducing a highly effective sono-catalytic therapy with an impressive tumor inhibition rate of 98.1%.Copyright © 2023. Published by Elsevier Ltd.