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Self-assembled albumin nanoparticles induce pyroptosis for photodynamic/photothermal/immuno synergistic therapies in triple-negative breast cancer

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机构： [1]School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. [2]Department of Ultrasound Medical Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. [3]Institute of Materia Medica, North Sichuan Medical College, Nanchong, Sichuan, China.

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关键词： triple-negative breast cancer pyroptosis phototherapy immunotherapy nanomedicine

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Triple-negative breast cancer (TNBC) is characterized by a high degree of malignancy, early metastasis, limited treatment, and poor prognosis. Immunotherapy, as a new and most promising treatment for cancer, has limited efficacy in TNBC because of the immunosuppressive tumor microenvironment (TME). Inducing pyroptosis and activating the cyclic guanosine monophosphate-adenosine monophosphate synthase/interferon gene stimulator (cGAS/STING) signaling pathway to upregulate innate immunity have become an emerging strategy for enhancing tumor immunotherapy. In this study, albumin nanospheres were constructed with photosensitizer-IR780 encapsulated in the core and cGAS-STING agonists/H2S producer-ZnS loaded on the shell (named IR780-ZnS@HSA). In vitro, IR780-ZnS@HSA produced photothermal therapy (PTT) and photodynamic therapy (PDT) effects. In addition, it stimulated immunogenic cell death (ICD) and activated pyroptosis in tumor cells via the caspase-3-GSDME signaling pathway. IR780-ZnS@HSA also activated the cGAS-STING signaling pathway. The two pathways synergistically boost immune response. In vivo, IR780-ZnS@HSA + laser significantly inhibited tumor growth in 4T1 tumor-bearing mice and triggered an immune response, improving the efficacy of the anti-APD-L1 antibody (aPD-L1). In conclusion, IR780-ZnS@HSA, as a novel inducer of pyroptosis, can significantly inhibit tumor growth and improve the efficacy of aPD-L1.Copyright © 2023 Yang, Guo, Huang, Bian, Zhang, Wei, He, Hu, Li, Zhou and Lu.

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出版当年[2023]版：

大类 | 2 区医学

小类 | 2 区免疫学

最新[2023]版：

大类 | 2 区医学

小类 | 2 区免疫学

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出版当年[2023]版：

Q1 IMMUNOLOGY

最新[2023]版：

Q1 IMMUNOLOGY

影响因子： 5.7 最新[2023版] 6.8 最新五年平均 5.7 出版当年[2023版] 6.8 出版当年五年平均 7.3 出版前一年[2022版]

第一作者：

第一作者机构： [1]School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. [2]Department of Ultrasound Medical Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

通讯作者：

通讯机构： [1]School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. [2]Department of Ultrasound Medical Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

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