Sodium Bicarbonate Nanoparticles for Amplified Cancer Immunotherapy by Inducing Pyroptosis and Regulating Lactic Acid Metabolism
Binbin Ding, Pan Zheng, Jia Tan, Hao Chen, Qi Meng, Jing Li, Xinyang Li, Di Han, Ziyao Li, Xinyu Ma, Ping’an Ma, Jun Lin
Abstract
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.