Sonocatalysis-responsive nanodrug platforms for radioimmunotherapy against breast cancer

•HAHf was developed which could produce H2/O2 and ROS in tumor microenvironment under soniciaftion.•Sonocatalysis-responsive HAHf modulated tumor hypoxia and enhance the effect of radiotherapy to breast cancer.•M1 repolarization was induced during HAHf mediated sonocatalysis.•Under sonication. HAHf improves radiotherapeutic efficacy and subsequent induce antitumor immunity. Immunosuppressive characteristic of the hypoxic tumor microenvironment (TME) is a major cause of tumor radioresistance in breast cancer. To address these therapeutic limitations, a self-assembled nanodrug platform consistent of hafnium-bonded hemin (HAHf) was designed to improve TME suppression via controlled sonocatalysis-induced O2 and H2 release. Under ultrasonication (US), the HAHf nanoparticles were able to overcome intratumoral hypoxia by converting abundant H2O2 within the TME to O2. Meanwhile, H2 gas was generated during the process and cytotoxic reactive oxygen species (ROS) were produced. These effects promoted the pro-inflammatory M1 polarization of tumor-associated macrophages while also driving the generation of high levels of pro-inflammatory cytokines. The presence of hafnium in the HAHf nanoparticles can enhance local energy decomposition in the target tumor. When utilized in combination with radiotherapy and sonocatalysis-mediated gas therapy, the HAHf particles enhanced the death of immunogenic tumor cells, promoted dendritic cell (DC) maturation, and improved intratumoral infiltration of cytotoxic T cells, ultimately overcoming the immunosuppressive TME and inhibiting tumor growth. The nanodrug platform developed in this study has significant potential as a basis for future therapeutic approaches using sonocatalysis to enhance the efficiency of radioimmunotherapy in the treatment of breast cancers.