Defect-Rich Platinum-Zinc Oxide Heterojunction as a Potent ROS Amplifier for Synergistic Sono-Catalytic Therapy.

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 HO into a large number of O 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 (O) 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 HO into a large quantity of O 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%.