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

Abstract

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 complex 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.