A Z-scheme heterojunction sonozyme for enhanced sonodynamic and chemodynamic therapy through cascade amplification of ROS generation

The differential rate of reactive oxygen species (ROS) in cascade amplification can significantly improve the efficacy of sonodynamic/chemodynamic therapy (SDT/CDT). However, the currently developed sonozyme system composed of sonosensitizers and nanozymes not only has problems with low efficiency and poor stability, but also is limited by the abominable tumor microenvironment (TME). On this basis, we report a novel ROS yield cascade amplification strategy that combines the enhancement of sonosensitizer/nanozyme activity and regulation of TME. A bandgap-matched Z-scheme heterojunction with improved electron-hole separation kinetics is constructed by integrating biocompatible carbon dots (CDs) and Fe-based metal–organic frameworks (Fe-MOF). Using CDs as an auxiliary semiconductor can sensitize Fe-MOF by inhibiting the recombination of US-activated electron-hole pairs and accelerating the electron transfer efficiency, thereby enhancing the various enzyme-like simulated activities of Fe-MOF. Endowed with these advantages, the CD@Fe-MOF nanocomposite realizes cascade amplification of ROS production, which is achieved through enhancing SDT/CDT efficacy, scavenging glutathione GSH, and relieving tumor hypoxia. When CD@Fe-MOF is administered intravenously followed by US irradiation on tumor tissues, the constructed Z-scheme heterojunction nanoplatform enables complete tumor eradication with no recurrence. Overall, this study verifies the feasibility of using CDs as auxiliary semiconductors to sensitize sonosensitizers and nanozymes, while also offering novel insights for heterojunction engineering in tackling malignant tumors.