4.8 Article

Designing Lactate Dehydrogenase-Mimicking SnSe Nanosheets To Reprogram Tumor-Associated Macrophages for Potentiation of Photothermal Immunotherapy

期刊

ACS APPLIED MATERIALS & INTERFACES
卷 14, 期 24, 页码 27651-27665

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acsami.2c05533

关键词

acidic tumor microenvironment; macrophage polarization; nanozyme; antitumor; immunotherapy

资金

  1. National Natural Science Foundation of China [21877049, 32171296]
  2. Guangdong Natural Science Foundation [2020B1515120043]
  3. Major Program for Tackling Key Problems of Industrial Technology in Guangzhou [201902020013]
  4. Special Funds for the Cultivation of Guangdong College Students Scientific and Technological Innovation [pdjh2021b0059]

向作者/读者索取更多资源

This study proposes a feasible therapeutic strategy for depleting lactate and reconstructing an immunosuppressive tumor microenvironment using Se-containing nanosheets, which can restore the potent tumor-killing activity of macrophages, thereby amplifying the effects of TAM-based antitumor immunotherapy.
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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