Sonodynamic and chemodynamic therapy (SDT/CDT) based on the production of high cytotoxicity reactive oxygen species (ROS) for killing cancer cells are promising tumor treatment modalities owing to their non-invasiveness, specificity, and high penetration depth. Nevertheless, sonosensitizers and nanozymes (sonozymes) frequently encounter issues with low ROS production efficiency and limited tumor microenvironment (TME) susceptibility. Herein, we report for the first time the fabrication of Cu nanoparticle (NP) sensitized oxygen-deficient MnO 2-x nanoflower sonozymes (Cu/MnO 2-x ) to achieve the cascade amplification of ROS production. The loading of Cu NPs can not only suppress the recombination of US-activated electron-hole pairs owing to the formation of Schottky junction within Cu/MnO 2-x , but also enhance the multienzyme-mimic activity of MnO 2-x by accelerating electron transfer efficiency. Cu/MnO 2-x sonozymes realize cascade amplification of ROS production through the enhancement of SDT/CDT performances, consumption of GSH, and alleviation of tumor hypoxia. Complete elimination of tumor tissues without any chance of recurrence is accomplished by injecting Cu/MnO 2-x intravenously and using US irradiation on the tumor tissues. This work demonstrates the potential of Cu NPs as auxiliary sonozymes for the sensitization of sonosensitizers and nanozymes, providing new perspectives for combining the advantages of SDT with CDT to address TME constraints.
Shi et al. (Sun,) studied this question.