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

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 TiO2-Fe3O4@PEG Janus nanostructure composed of the typical sonosensitizer TiO2 and nanoenzyme Fe3O4 is rationally designed and engineered for bilaterally enhanced SDT and chemodynamic therapy (CDT). The deposition of Fe3O4 component on the surface of TiO2 can not only endow the Janus nanosonosensitizers with Fenton-catalytic activity to generate hydroxyl radicals (center dot OH) from tumor-endogenous overexpressed H2O2 for CDT but also enhance the SDT performance of TiO2 via narrowing the band gap of TiO2 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.

Automated summary

In this study, a TiO2-Fe3O4@PEG Janus nanostructure was designed and engineered for bilaterally enhanced SDT and CDT. The rational design not only improved the treatment efficacy but also addressed the major concerns of SDT, providing a promising approach for non-invasive therapy.