Trienzyme-like Co3O4@TiO2-xnanozymes for heterojunction-enhanced nanocatalytic-sonodynamic tumor therapy

Nanozymes have shown promising potential in cancer therapy owing to the advantages of low-cost, excellent stability, and high reproducibility. However, the inherent low catalytic activity of nanozymes and highly com-plex tumor microenvironment (TME) severely restricted the clinical applications of nanocatalytic therapy. Herein, we first reported a heterojunction (HJ)-enhanced nanocatalytic-sonodynamic therapy platform based on Co3O4@TiO2-x Z-scheme HJs by depositing Co3O4 nanoparticles (NPs) onto TiO2-x nanosheets (NSs). Co3O4@-TiO2-x HJs not only exhibited excellent ultrasound (US)-triggered reactive oxygen species (ROS) generation ability, but also possessed triple enzyme-mimic activities (peroxidase-mimic, catalase-mimic, and GSH depletion activities) to realize the amplification of ROS levels and relieve tumor hypoxia. More importantly, the triple enzyme-mimic activities and sonodynamic properties of single-component Co3O4 or TiO2-x were greatly enhanced by the construction of Z-scheme HJs owing to the accelerate carrier transfer process and improved spatial separation dynamics of US-generated electron-hole pairs. The synergetic therapeutic effect of Co3O4@-TiO2-x through HJ-enhanced nanocatalytic-sonodynamic therapy could achieve complete tumor eradication without recurrence. Our work will open up a promising approach to engineer semiconductor HJs with both sonodynamic and enzyme-mimic activities for enhanced nanocatalytic-sonodynamic combination therapy.

Automated summary

In this study, a heterojunction-enhanced nanocatalytic-sonodynamic therapy platform based on Co3O4@TiO2-x Z-scheme heterojunctions was reported. The platform possesses ultrasound-triggered ROS generation ability and triple enzyme-mimic activities, resulting in amplified ROS levels and relief of tumor hypoxia. The construction of Z-scheme heterojunctions effectively enhances the enzyme-mimic activities and sonodynamic properties, leading to complete tumor eradication. This work opens up a promising approach for the development of semiconductor heterojunctions with both sonodynamic and enzyme-mimic activities for enhanced nanocatalytic-sonodynamic combination therapy.