Enhanced radiotherapy efficacy and induced anti-tumor immunity in HCC by improving hypoxia microenvironment using oxygen microcapsules

•A facile method of preparing nanoparticle-stabilized oxygen microcapsules for oxygen delivery.•Combined treatments of oxygen microcapsules and radiotherapy are effective for anti-tumor therapy.•Synergetic therapy reduces the TAMs and activates anti-tumor immune responses. Hypoxia represents a tremendous barrier for effective radiotherapy in hepatocellular carcinoma (HCC). Treatment strategies for improving hypoxia are of great significance to enhance radiotherapy efficacy. Here, we design polydopamine-nanoparticle-stabilized oxygen microcapsules by interfacial polymerization, which encapsulate oxygen in the core of polydopamine nanoparticle shell, exhibiting excellent biocompatibility and dispersity in aqueous solution. The oxygen microcapsules rapidly increase the oxygen concentration in hypoxia environment and maintain the oxygen concentration for a long time, indicating as an excellent and stable oxygen delivery carrier. Using a mouse model of HCC, local injection of oxygen microcapsules can significantly enhance radiotherapy efficacy. Combined treatments using oxygen microcapsules and radiotherapy reduce the number of tumor associated macrophages (TAMs) while reshaping the pro-tumor M2-type TAMs into anti-tumor M1-type polarization, thus activating T-cell-mediated anti-tumor immune responses (the accumulation of help T lymphocyte 1 cells and cytotoxic T cells) by improving hypoxia in tumors. The results suggest that combined therapy using oxygen microcapsules and radiotherapy, which improves hypoxia in tumors, is a promising strategy against HCC.