Oxygen-Deficient Black Titania for Synergistic/Enhanced Sonodynamic and Photoinduced Cancer Therapy at Near Infrared-II Biowindow

The conventional inorganic semiconductors are not suitable for in vivo therapeutic nanomedicine because of the lack of an adequate and safe irradiation source to activate them. This work reports on the rational design of titania (TiO₂)-based semiconductors for enhanced and synergistic sono-/photoinduced tumor eradication by creating an oxygen-deficient TiO_{2- x} layer onto the surface of TiO₂ nanocrystals, which can create a crystalline-disordered core/shell structure (TiO₂@TiO_{2- x}) with black color. As found in the lessons from traditional photocatalysis, such an oxygen-deficient TiO_{2- x} layer with abundant oxygen defects facilitates and enhances the separation of electrons (e^-) and holes (h⁺) from the energy-band structure upon external ultrasound irradiation, which can significantly improve the efficacy of sono-triggered sonocatalytic tumor therapy. Such an oxygen-deficient TiO_{2- x} layer can also endow black titania nanoparticles with high photothermal-conversion efficiency (39.8%) at the NIR-II biowindow (1064 nm) for enhanced photothermal hyperthermia. Both in vitro cell level and systematic in vivo tumor-bearing mice xenograft evaluations have demonstrated the high synergistic efficacy of combined and enhanced sonodynamic therapy and photothermal ablation as assisted by oxygen-deficient black titania, which has achieved complete tumor eradication with high therapeutic biosafety and without obvious reoccurrence. This work not only provides the paradigm of high therapeutic efficacy of a combined sono-/photoinduced tumor-treatment protocol but also significantly broadens the nanomedical applications of semiconductor-based nanoplatforms by rational design of their nanostructures and control of their physiochemical properties.