Sodium Bicarbonate Nanoparticles for Amplified Cancer Immunotherapy by Inducing Pyroptosis and Regulating Lactic Acid Metabolism

Abstract Although immunotherapy has a broad clinical application prospect, it is still hindered by low immune responses and immunosuppressive tumor microenvironment. Herein, a simple and drug‐free inorganic nanomaterial, alkalescent sodium bicarbonate nanoparticles (NaHCO 3 NPs), is prepared via a fast microemulsion method for amplified cancer immunotherapy. The obtained alkalescent NaHCO 3 regulates lactic acid metabolism through acid‐base neutralization so as to reverse the mildly acidic immunosuppressive tumor environment. Additionally, it can further release high amounts of Na + ions inside tumor cells and induce a surge in intracellular osmolarity, and thus activate the pyroptosis pathway and immunogenic cell death (ICD), release damage‐associated molecular patterns (DAMPs) and inflammatory factors, and improve immune responses. Collectively, NaHCO 3 NPs observably inhibit primary/distal tumor growth and tumor metastasis through acid neutralization remitted immunosuppression and pyroptosis induced immune activation, showing an enhanced antitumor immunity efficiency. This work provides a new paradigm for lactic acid metabolism and pyroptosis mediated tumor treatment, which has a potential for application in clinical tumor immunotherapy.