Tumour microenvironment-responded Fe-doped carbon dots-sensitized cubic Cu2O for Z-scheme heterojunction-enhanced sono-chemodynamic synergistic tumor therapy

The efficacy of electron-hole separation in a single sonosensitizer and the complexities of the tumor microenvironment (TME) present significant challenges to the effectiveness of sonodynamic therapy (SDT). Designing efficient sonosensitizers to enhance electron-hole separation and alleviate TME resistance is crucial yet challenging. Herein, we introduce a novel Z-scheme heterojunctions (HJs) sonosensitizer using Fe-doped carbon dots (CDs) as auxiliary semiconductors to sensitize cubic Cu₂O (Fe-CDs@Cu₂O) for the first time. Fe-CDs@Cu₂O demonstrated enhanced SDT effects due to improved electron-hole separation. Additionally, the introduction of Fe ions in CDs synergistically enhances Fenton-like reactions with Cu ions in Cu₂O, resulting in enhanced chemodynamic therapy (CDT) effects. Moreover, Fe-CDs@Cu₂O exhibited rapid glutathione (GSH) depletion, effectively mitigating TME resistance. With high rates of ¹O₂ and OH generated by Fe-CDs@Cu₂O, coupled with strong GSH depletion, single drug injection and ultrasound (US) irradiation effectively eliminate tumors. This innovative heterojunction sonosensitizer offers a promising pathway for clinical anti-tumor treatment.