肿瘤微环境
癌症研究
免疫疗法
体内
糖酵解
乳酸脱氢酶
癌症免疫疗法
巨噬细胞
免疫系统
材料科学
生物
生物化学
免疫学
体外
新陈代谢
酶
肿瘤细胞
生物技术
作者
Jiabao Ling,Yanzhou Chang,Zhongwen Yuan,Qi Chen,Lizhen He,Tianfeng Chen
标识
DOI:10.1021/acsami.2c05533
摘要
Rapid glycolysis of tumor cells produces excessive lactate to trigger acidification of the tumor microenvironment (TME), leading to the formation of immunosuppressive TME and tumor-associated macrophage (TAM) dysfunction. Therefore, reprogramming TAMs by depleting lactate with nanodrugs is expected to serve as an effective means of tumor-targeted immunotherapy. Herein, we report the use of lactic acid dehydrogenase (LDH)-mimicking SnSe nanosheets (SnSe NSs) loaded with a carbonic anhydrase IX (CAIX) inhibitor to reconstruct an acidic and immunosuppressive TME. As expected, this nanosystem could reprogram the TAM to achieve M1 macrophage activation and could also restore the potent tumor-killing activity of macrophages while switching their metabolic mode from mitochondrial oxidative phosphorylation to glycolysis. In addition, the repolarizing effect of SnSe NSs on macrophages was validated in a coculture model of bone marrow-derived macrophages, in three patient-derived malignant pleural effusion and in vivo mouse model. This study proposes a feasible therapeutic strategy for depleting lactate and thus ameliorating acidic TME employing Se-containing nanosheets, which could further amply the effects of TAM-based antitumor immunotherapy.
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