Engineering Janus Chemoreactive Nanosonosensitizers for Bilaterally Augmented Sonodynamic and Chemodynamic Cancer Nanotherapy

Abstract As a non‐invasive treatment modality with high tissue‐penetration depth, ultrasound‐triggered sonodynamic therapy (SDT) has been extensively explored and is regarded as the alternative choice to overcome the drawbacks of conventional photo‐triggered therapies. Nevertheless, the low quantum yield of sonosensitizer, tumor hypoxia, and undesirable therapeutic efficiency are still the major concerns of SDT. It is highly challenging but necessary to explore the SDT‐based synergistic, augmented, and noninvasive therapeutic modalities. Herein, a distinct TiO 2 Fe 3 O 4 @PEG Janus nanostructure composed of the typical sonosensitizer TiO 2 and nanoenzyme Fe 3 O 4 is rationally designed and engineered for bilaterally enhanced SDT and chemodynamic therapy (CDT). The deposition of Fe 3 O 4 component on the surface of TiO 2 can not only endow the Janus nanosonosensitizers with Fenton‐catalytic activity to generate hydroxyl radicals (•OH) from tumor‐endogenous overexpressed H 2 O 2 for CDT but also enhance the SDT performance of TiO 2 via narrowing the band gap of TiO 2 and reducing the recombination rate of the electrons (e – /h + ) pair. In turn, the US activation can both accelerate mass transfer and chemical reaction rates of the Fenton reaction to enhance the CDT effect. The high efficacy of bilaterally enhanced SDT and CDT is systematically demonstrated both in vitro and in vivo.