MXene-based nanozymes remodel tumor microenvironment for heterojunction-enhanced sonodynamic and chemodynamic therapy to boost robust cancer immunotherapy

Reactive oxygen species (ROS)-mediated sonodynamic therapy (SDT) holds increasing potential in treating deepseated tumor owing to the high tissue-penetration depth, but hardly controls remote metastasis. To trigger robust cancer immunotherapy against malignant metastatic cancers, we report the rational construction of Z-scheme heterojunctions through decorating biocompatible Co3O4 nanoparticles with multiple enzyme-like catalytic activities onto Ti3C2Tx nanosheets to realize the augmented SDT and chemodynamic therapy (CDT). The deposition of Co3O4 nanoparticles not only sensitizes the sonodynamic activity of Ti3C2Tx nanosheets owing to the regulation of separation dynamics of electron-hole pairs, but also achieves the cascade amplification of ROS generation through Co2+-mediated Fenton-like reaction, Co3+-facilitated GSH depletion, and catalytic decomposition of endogenous H2O2 to relieve hypoxia. More importantly, the immunosuppressive TME could be reversed by the greatly enhanced ROS levels, ultimately inducing immunogenic cell death that promotes robust systemic immune responses. The heterojunction-enhanced SDT and CDT via Co3O4@Ti3C2Tx could trigger robust cancer immunotherapy, which achieves the eradication of primary tumors and suppression of distant tumors. This work highlights the potential of heterojunction engineering-enhanced SDT and CDT to trigger robust cancer immunotherapy.