Bimetallic Cu@Ru Core-Shell Structures with Ligand Effects for Endo-Exogenous Stimulation-Mediated Dynamic Oncotherapy.

Dynamic therapies, which induce reactive oxygen species (ROS) production in situ through endogenous and exogenous stimulation, are emerging as attractive options for tumor treatment. However, the complexity of the tumor substantially limits the efficacy of individual stimulus-triggered dynamic therapy. Herein, bimetallic copper and ruthenium (Cu@Ru) core-shell nanoparticles are applied for endo-exogenous stimulation-triggered dynamic therapy. The electronic structure of Cu@Ru is regulated through the ligand effects to improve the adsorption level for small molecules, such as water and oxygen. The core-shell heterojunction interface can rapidly separate electron-hole pairs generated by ultrasound and light stimulation, which initiate reactions with adsorbed small molecules, thus enhancing ROS generation. This synergistically complements tumor treatment together with ROS from endogenous stimulation. In vitro and in vivo experiments demonstrate that Cu@Ru nanoparticles can induce tumor cell apoptosis and ferroptosis through generated ROS. This study provides a new paradigm for endo-exogenous stimulation-based synergistic tumor treatment.