Bacteria outer membrane-based oxygen gels alleviate tumor hypoxia for enhanced systemic immune response to radiotherapy

Radiotherapy (RT) is considered a standard cancer treatment that directly kills tumor cells and promotes a systemic immune response. However, RT may also lead to tumor hypoxia, which further inhibits the antigen-presenting function of dendritic cells (DCs) and thereby weakens the systemic anti-tumor immune response induced by radiotherapy. In this study, the oxygen-loaded in situ gels carrying bacterial outer membrane (MOGel) were synthesized. As the gels slowly degraded, oxygen was gradually released to alleviate tumor hypoxia. The released bacterial outer membrane (OM) continuously activated DCs, enhancing their antigen-presenting capability. The results demonstrated that MOGel combined with RT induced the strongest tumor cell apoptosis in vitro and achieved a 80% tumor suppression rate in a colon cancer orthotopic model. Importantly, MOGel+RT induced an enhanced abscopal effect, and hypoxia and enhanced DCs activation contributed to the systemic immune response. Thus, OM-based oxygen gels may offer a novel strategy for enhancing the systemic immune response to RT.