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-xO@TiO2-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 (O-1(2)) and hydroxyl radicals (& BULL;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 & BULL;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.

Automated summary

This study developed a novel heterojunction nanosonosensitizer with enhanced production of singlet oxygen and hydroxyl radicals for sonodynamic therapy. The nanosonosensitizer effectively separated the electron-hole pairs generated by ultrasound through a direct Z-scheme charge transfer mechanism. The experiments demonstrated complete tumor eradication in osteosarcoma models using a single drug injection and single ultrasound irradiation.