Band-interface cooperative engineering of bismuth-based heterojunctions for sonodynamic-chemodynamic synergistic breast cancer therapy

The clinical efficacy of sono-immunotherapy is limited by the low reactive oxygen species (ROS) yield of sonosensitizers and the antioxidant defense mechanisms within the tumor microenvironment (TME). Herein, leveraging bandgap and interfacial engineering strategies, we fabricate a bismuth-based nanoheterojunction BiF₃:Ce-BiOI-PEG (BCOP) via an ion-exchange method. BCOP integrates efficient sono-catalytic ROS generation with TME-responsive Fenton-like catalytic activity, enabling synergistic enhancement of sonodynamic therapy (SDT) and chemodynamic therapy (CDT). Under ultrasound (US) irradiation, the BCOP heterojunction significantly boosts ROS production efficiency by utilizing its built-in electric field to drive directional carrier separation. Concurrently, the acidic TME triggers a Ce³⁺-mediated Fenton-like reaction, converting endogenous H₂O₂ into highly toxic hydroxyl radicals (•OH). Furthermore, dual glutathione (GSH) depletion via Bi³⁺ coordination coupled with hole (h⁺)-mediated oxidation effectively impairs the antioxidant capacity of the TME, synergistically amplifying oxidative stress-induced damage in tumor cells. In vitro cell experiments demonstrate that BCOP induces mitochondrial damage, apoptosis, and immunogenic cell death (ICD) in breast cancer cells. In vivo studies further confirm its ability to activate a systemic anti-tumor immune response and markedly inhibit tumor growth. This study provides a band-interfacial cooperative regulation strategy for multimodal tumor immunotherapy.