期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 16, 期 -, 页码 1913-1926出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S297933
关键词
breast cancer; immune response; phase-transformation nanoparticles; immunogenic cell death; DC maturation
资金
- National Key R&D Program of China [2018YFC0115204]
- National Natural Science Foundation of China [81672634]
- CSCO Pilot Oncology Research Fund [Y-2019AZMS-0377]
- Capital Health Development Research Project [2018-2-4023]
- Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences Clinical and Translational Medicine Research [12019XK320071]
Nanoparticle-mediated sonodynamic therapy can promote anti-tumor immune response of breast cancer cells by inhibiting cell proliferation, promoting apoptosis, increasing CD4 and CD8 T cell subsets, and reducing PD-1 positive T cells, leading to suppressed tumor growth.
Purpose: Immunologically quiescent of breast cancer cells has been recognized as the key impediment for the breast cancer immunotherapy. In this study, we aimed to investigate the role of nanoparticle-mediated sonodynamic therapy (SDT) in promoting anti-tumor immune of breast cancer cells and its potential immune mechanisms. Materials and Methods: The phase-transformation nanoparticles (LIP-PFH nanoparticles) were in-house prepared and its physiochemical characters were detected. The CCK-8 assay, apoptosis analysis and Balb/c tumor model establishment were used to explore the anti-tumor effect of LIP-PFH nanoparticles triggered by low-intensity focused ultrasound (LIFU) both in vitro and in vivo. Flow cytometry and immunohistochemistry of CD4(+)T, CD8(+)T, CD8(+)PD-1(+)T in blood, spleen and tumor tissue were performed to represent the change of immune response. Detection of immunogenic cell death (ICD) markers was examined to study the potential mechanisms. Results: LIP-PFH nanoparticles triggered by LIFU could inhibit the proliferation and promote the apoptosis of 4T1 cells both in vitro and in vivo. CD4(+)T and CD8(+)T cell subsets were significantly increased in blood, spleen and tumor tissue, meanwhile CD8(+)PD-1(+)T cells were reduced, indicating enhancement of anti-tumor immune response of breast cancer cells in the nanoparticle-mediated SDT group. Detection of ICD markers (ATP, high-mobility group box Bl, and calreticulin) and flow cytometric analysis of dendritic cell (DC) maturity further showed that the nanoparticle-mediated SDT can promote DC maturation to increase the proportion of cytotoxic T cells by inducing ICD of breast cancer cells. Conclusion: The therapy of nanoparticles-mediated SDT can effectively enhance anti-tumor immune response of breast cancer.
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