Ultrasound-enhanced dual-responsive bismuth nanocatalysts for alleviating tumor hypoxia and promoting breast cancer sonodynamic-immunotherapy

Sonodynamic therapy (SDT) has emerged as a promising approach in cancer treatment due to its noninvasive nature and high specificity. However, its catalytic efficacy is limited by challenges such as tumor microenvironment (TME) hypoxia and inefficient reactive oxygen species (ROS) generation. To address these limitations, a bismuth-based nanocatalyst, BiOCl:Ce-Pt@PGA (BCCP), responsive to both the TME and ultrasound (US), was developed to enhance the antitumor effects of SDT by ameliorating hypoxia. Under US stimulation, BCCP facilitates oxygen generation through oxygen evolution reaction (OER) and mimics peroxidase activity to catalyze the conversion of H2O2 to O2, effectively alleviating tumor hypoxia. This dual in situ oxygen-generating strategy ensures a sufficient oxygen supply for SDT. Concurrently, BCCP generates ROS via sonocatalysis, and the doping of Ce ions further accelerates ROS production through Fenton-like reactions, intensifying oxidative stressinduced damage in breast tumors. Additionally, BCCP depletes glutathione (GSH) in the TME, induces immunogenic cell death (ICD), promotes dendritic cell maturation, and enhances T-cell infiltration, thereby stimulating antitumor immune responses. Through a dual-response strategy targeting the TME and US, BCCP significantly inhibits tumor growth and activates the immune system to suppress lung metastasis. This study introduces a novel tandem therapeutic strategy and provides new insights into activatable SDT.