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 CDTnanoadjuvants platform (Se@OMV-GOx-HA) by modifying probiotic-derived selenium (Se) nanoparticles with glucose oxidase (GOx) and hyaluronic acid (HA) to boost alpha PD-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 center dot 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 center dot 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 alpha PD-L1-medaited ICB therapy. Given the clinical available of HBO, this nanosystem has great clinical translation potential for cancer CDT/immunotherapy.