Hyperbaric oxygen augments chemodynamic effect induced by probiotic-derived selenium nanoparticles to enhance cancer immune checkpoint blockade therapy

Chemodynamic therapy (CDT) was a promising approach to enhance the immunogenicity of tumor cells for potentiating immune checkpoint blockade (ICB) therapy, but usually suffered from hypoxia and immunosuppressive tumor microenvironment. Herein, we developed a hyperbaric oxygen (HBO)-strengthened CDT-nanoadjuvants platform (Se@OMV-GOx-HA) by modifying probiotic-derived selenium (Se) nanoparticles with glucose oxidase (GOx) and hyaluronic acid (HA) to boost αPD-L1-medaited ICB therapy against breast cancer. In the presence of H2O2 and glutathione (GSH), Se@OMV acted as nanoenzyme to mediate the electron transfer from GSH to O2 giving O2–, while GOx catalyzed the production of H2O2. Synergistically, HBO effectively improved tumor hypoxia to foster GOx-catalyzed oxidation of glucose to H2O2, then provided the essential fuels including H2O2 and O2 for Se-mediated O2– generation, causing strong immunogenic cell death (ICD) effect to enhance the immunogenicity of tumor cells. Under co-stimulation by Se@OMV acting as immunoadjuvants, maturation of dendritic cells and priming of cytotoxic T cells were largely promoted. Assisted by HBO, infiltration of cytotoxic T cells in mice tumor was significantly improved, which not only generated long-term antitumor immune memory, but largely boosted αPD-L1-medaited ICB therapy. Given the clinical available of HBO, this nanosystem has great clinical translation potential for cancer CDT/immunotherapy.