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

被引：70

作者：

Ding, Binbin ^{[1
,2
]}

Zheng, Pan ^{[1
,3
]}

Tan, Jia ^{[1
,2
]}

Chen, Hao ^{[1
,2
]}

Meng, Qi ^{[1
,2
]}

Li, Jing ^{[1
,2
]}

Li, Xinyang ^{[1
,2
]}

Han, Di ^{[1
,2
]}

Li, Ziyao ^{[1
,2
]}

Ma, Xinyu ^{[1
,2
]}

Ma, Ping'an ^{[1
,2
]}

Lin, Jun ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, State Key Lab Rare Earth Resource Utilizat, Changchun Inst Appl Chem, Changchun 130022, Peoples R China

[2] Univ Sci & Technol China, Sch Appl Chem & Engn, Hefei 230026, Peoples R China

[3] Harbin Engn Univ, Key Lab Superlight Mat & Surface Technol, Minist Educ, Coll Mat Sci & Chem Engn, Harbin 150001, Peoples R China

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2023年 / 62卷 / 40期

基金：

中国国家自然科学基金;

关键词：

Immunosuppressive Tumor Microenvironment; Immunotherapy; Lactic Acid Metabolism; NaHCO3; Nanoparticle; Pyroptosis; TUMOR MICROENVIRONMENT; LACTATE;

D O I：

10.1002/anie.202307706

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 (NaHCO3 NPs), is prepared via a fast microemulsion method for amplified cancer immunotherapy. The obtained alkalescent NaHCO3 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, NaHCO3 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.

引用

页数：8

共 32 条

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