Cu2-xO@TiO2-y Z-scheme heterojunctions for sonodynamic-chemodynamic combined tumor eradication

It is urgent to develop high-efficacy nanosonosensitizers with enhanced charge transfer and tumor microenvironment regulation capabilities for sonodynamic therapy (SDT). A novel heterojunction nanosonosensitizer Cu2-x[email protected]2-y was designed from core-shell oxide semiconductors with narrow bandgaps (2.1–2.2 eV) using positively charged Cu2-xO nanodots and negatively charged TiO2-y nanosheets as components. The ultrasound (US) triggered singlet oxygen (1O2) and hydroxyl radicals (•OH) generation rates notably increased compared with single components, which can be ascribed to a direct Z-scheme charge transfer mechanism that greatly improved spatial separation dynamics of US-generated electron-hole pairs. Moreover, the Cu+-Cu2+ redox cycle not only catalyzed the Fenton like reaction to generate •OH from tumor endogenous H2O2 but also depleted endogenous glutathione (GSH). Human osteosarcoma models showed complete tumor eradication by single drug injection and single US irradiation. This work highlights non-stoichiometric oxide heterostructures with the Z-scheme charge transfer mechanism for chemodynamic-sonodynamic combined therapy.