Journal
FRONTIERS IN IMMUNOLOGY
Volume 14, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2023.1173487
Keywords
triple-negative breast cancer; pyroptosis; phototherapy; immunotherapy; nanomedicine
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Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with limited treatment options and poor prognosis. This study developed albumin-based nanospheres loaded with a photosensitizer and cGAS-STING agonists, which showed effectiveness in inducing pyroptosis, a form of immunogenic cell death, and activating the cGAS-STING signaling pathway. In vivo experiments demonstrated that this novel strategy inhibited tumor growth and enhanced the efficacy of anti-PD-L1 antibody treatment in TNBC.
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.
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