Type-II Bi ₂ Fe ₄ O ₉ –Black Phosphorus Nanocomposite Heterojunction for Chemodynamic-Enhanced Radiodynamic Cancer Therapy

Despite advances in radiodynamic therapy (RDT), its efficacy remains limited by tumor hypoxia and glutathione (GSH)-mediated radioresistance. Herein, we developed a poly(allylamine hydrochloride)-modified Bi2Fe4O9-black phosphorus (BFO-BP) nanocomposite heterojunction via hydrothermal synthesis to enable synergistic radiotherapy/radiodynamic therapy/enhanced chemodynamic therapy/photothermal therapy (RT/RDT/ECDT/PTT). The BFO-BP nanoplatform exhibited dual functionality: (1) catalytic decomposition of tumor-overexpressed H2O2 into O2 to alleviate hypoxia, and (2) X-ray-triggered Fe3+/Fe2+ cycling that enhanced •OH generation while depleting GSH. Spectroscopic and microscopic characterizations confirmed the formation of a type-II heterojunction, which facilitated charge separation and amplified reactive oxygen species (ROS) production under irradiation (EPR signal intensity increased 4.3-fold vs BP). The nanoplatform demonstrated exceptional photothermal conversion efficiency (ΔT = 61 °C at 100 ppm) and radiation-boosted Fenton activity. In 4T1 tumor-bearing mice, combined RT/RDT/ECDT/PTT treatment suppressed tumor growth by 93.3% compared to controls, with no observed systemic toxicity. This work presents a paradigm for overcoming tumor microenvironment constraints through multifunctional nanoplatform design.