Shell-core COF@Co3O4 Z-scheme heterojunctions for triple amplification of oxidative stress to enhance nanocatalytic-sonodynamic tumor therapy

Constructing efficient nanozyme platforms with multiple amplification of tumor oxidative stress is crucial to enhance the reactive oxygen species (ROS)-mediated tumor therapy. However, the inherent low catalytic activity and unsustainability of nanozymes in the highly complex tumor microenvironment (TME) severely restricted their clinical applications. Herein, we first reported a heterojunction (HJ)-enhanced nanocatalytic-sonodynamic therapy nanoplatform based on COF@Co3O4 Z-scheme HJs with shell-core architecture by coating COF on the surface of Co3O4 nanospheres. The as-prepared Co3O4 nanospheres not only exhibited excellent sonodynamic properties owing to the narrow bandgap (1.37 eV), but also possessed peroxidase-like, catalase-like, and glutathione peroxidase-like catalytic activities to realize the amplification of ROS levels and relieve tumor hypoxia due to the presence of multivalent Co element. More importantly, the ultrasound (US)-triggered ROS generation ability and triple enzyme-mimic activity of Co3O4 nanospheres were greatly enhanced by the encapsulation of COF to fabricate Z-scheme HJs with large interfacial contact area. Based on the improved spatial separation dynamics of US-generated electron-hole pairs and accelerate carrier transfer process, complete tumor eradication without recurrence was realized by the synergetic therapeutic effect of COF@Co3O4 through HJ-enhanced nanocatalytic-sonodynamic therapy. This work presents highly efficient nanozyme platforms with both multiple enzyme-mimic catalytic activity and sonodynamic properties, which will open up a promising approach to engineer semiconductor Z-scheme HJs for enhanced tumor therapy.