A Novel Pt–TiO2 Heterostructure with Oxygen‐Deficient Layer as Bilaterally Enhanced Sonosensitizer for Synergistic Chemo‐Sonodynamic Cancer Therapy

Sonodynamic therapy (SDT) activated by ultrasound is attractive as a potential alternative to conventional phototriggered therapies owing to the deeper penetration depth and the absence of phototoxicity. Nevertheless, the low quantum yield of nano‐sonosensitizer and the tumor hypoxia remain significant challenges for SDT. Herein, a novel TiO2‐based nano‐sonosensitizer is reported to bilaterally enhance the quantum yield by simultaneous integration of precious metal Pt nanoparticles (NPs) and an oxygen‐deficient layer. Furthermore, the hollow cavity of TiO2 serves as a reservoir to load doxorubicin, an anticancer drug for chemotherapy as well as a molecular sonosensitizer for SDT. The decorated Pt NPs act as nanozymes to catalyze the decomposition of endogenous hydrogen peroxide for the generation of oxygen to alleviate tumor hypoxia, reduce resistance to chemotherapy, and provide sufficient oxygen source for subsequently facilitating SDT‐induced reactive oxygen species production. The high chemo‐sonodynamic synergistic efficacy is systematically demonstrated both in vitro and in vivo. More importantly, it is believed that the novel design and the new finding in the synthesis of Pt–TiO2 heterostructures can be popularized for the preparation and application of the semiconductor‐based nanoplatforms in many fields. A novel Pt–TiO2 heterostructure is successfully constructed by simultaneous integration of noble metal Pt and an oxygen‐deficient layer to the TiO2 surface to bilaterally enhance the sonodynamic therapy effect. Meanwhile, with the assistance of Pt nanozyme and anticancer drugs as well as molecular sonosensitizer doxorubicin, the nanosystem achieves a strong synergistic therapeutic effect for oncotherapy.