Radiotherapy efficacy was greatly limited by hypoxia and overexpression of glutathione (GSH) in the tumor microenvironment (TME), which maintained the immunosuppressive microenvironment and promoted DNA repair. In this work, 4T1 cell membrane-coated Bi2-xMnxO3 nanospheres have been achieved via a facile protocol, which showed enhanced therapeutic efficacy for a combination of radiotherapy and immunotherapy. Bi2-xMnxO3 nanospheres showed appreciable performance in generating O2 in situ and depleting GSH to amplify DNA damage and remodel the tumor immunosuppressive microenvironment, thus enhancing radiotherapy efficacy. Cancer cell membrane-coated Bi2-xMnxO3 nanospheres (T@BM) prolonged blood circulation time and enriched the accumulation of the materials in the tumor. Meanwhile, the released Mn2+ could activate STING pathway-induced immunotherapy, resulting in the immune infiltration of CD8+ T cells on in situ mammary tumors and the inhibition of pulmonary nodules. As a result, approximately 1.9-fold recruitment of CD8+ T cells and 4.0-fold transformation of mature DC cells were observed compared with the phosphate-buffered saline (PBS) group on mammary tumors (in situ). In particular, the number of pulmonary nodules significantly decreased and the proliferation of pulmonary metastatic lesions was substantially inhibited, which provided a longer survival period. Therefore, T@BM exhibited great potential for the treatment of 4T1 tumors in situ and lung metastasis.
Keywords: Bi2−xMnxO3; DNA damage; cGAS−STING; radiosensitization; tumor hypoxia.