Metal-Phenolic Outer Membrane Vesicles for Cancer Radioimmunotherapy.

Bacterial outer membrane vesicles (OMVs) with catalase deposition have significant potential for cancer immunotherapy, yet their therapeutic efficiency is limited by insufficient immune activation. Metal ions with a high atomic number could act as radiosensitizers to increase radiation-dose deposition at tumor sites and boost the immunogenic effects of radiotherapy (RT). Herein, we report metal-phenolic OMVs by cloaking OMVs with hafnium (Hf)-phenolic networks (Hf-OMVs) for enhanced cancer radioimmunotherapy. In tumor microenvironment, catalase deposited in the envelope of OMVs initiated the decomposition of hydrogen peroxide to produce oxygen, resulting in hypoxia relief. Meanwhile, the Hf reinforced the accumulation of ionizing radiation at the tumor site, thereby inducing tumor cell death and releasing tumor antigens. In addition, the OMVs with immunomodulatory performance combined with released tumor antigens to promote dendritic cell maturation, thus enhancing T cell activation and eliciting potent antitumor immunity. In breast cancer mouse models, the Hf-OMVs effectively accumulated at the tumor site following intravenous injection and significantly delayed the growth of primary and distant tumors when combined with RT. Our work provides an organic/inorganic hybrid platform bridging the superiority of natural OMVs and synthetic Hf-phenolic networks for enhanced cancer radioimmunotherapy.