Ternary CD/Co3O4@MnCo2O4 heterojunction nanozymes for enhanced sonodynamic/NIR–II–photothermal/nanocatalytic therapy through triple amplification of ROS generation

Abstract

The therapeutic potential of nanozyme-based tumor catalytic therapy (NCT) has been widely recognized, yet its efficacy is compromised by the low-efficiency single-component nanozymes and multiple factors within the tumor microenvironment (TME) including adequate levels of H₂O₂ and overexpressed GSH milieu. Herein, the mild NIR-II hyperthermia and heterojunction fabrication co-augmented NCT strategy are first presented to realize the triple amplification of ROS generation. To demonstrate this concept, a novel ternary heterojunction nanozyme termed CD/Co₃O₄@MnCo₂O₄ (CD/CMCO) is successfully constructed through depositing nitrogen-doped carbon dots (CDs) on core-shell structural Co₃O₄@MnCo₂O₄ Z-scheme heterojunctions. The formed ternary CD/CMCO heterojunctions could be adopted as a US and NIR-II light double-responsive theranostic nanoplatform for simultaneous sonodynamic/NIR–II–photothermal/nanocatalytic therapy. Notably, the sonodynamic and NIR-II photothermal performances as well as the triple enzyme-like catalytic activities of Co₃O₄@MnCo₂O₄ and CDs can be enhanced by the construction of ternary heterojunctions owing to the optimized separation and migration of carriers. More interestingly, CD/CMCO with outstanding NIR-II photothermal characteristics enables the attainment of moderately elevated temperatures (∼43 °C), further amplifying the catalytic activities and then improving ROS generation. The triple cascade amplification of ROS generation is achieved by CD/CMCO with exceptional enzyme-like catalytic activities, which produced more ROS through alleviating hypoxia and consuming GSH. These favorable advantages of CD/CMCO enable it to be a triple ROS generation accelerator for heterojunction and mild NIR-II hyperthermia co-augmented synergistic tumor therapy. This work paves a novel avenue for exploring efficient tumor treatment based on ternary heterojunction nanozymes that are responsive to US and NIR-II light.