Phase-Transformation Nanoparticle-Mediated Sonodynamic Therapy: An Effective Modality to Enhance Anti-Tumor Immune Response by Inducing Immunogenic Cell Death in Breast Cancer

• DOI: 10.2147/ijn.s297933
• Publication Date: 2021-03-04T22:25:57Z
• Authors: Yiran Si; Jian Yue; Zhaoyang Liu; Mo Li; Feng Du; Xue Wang; Zhong Dai; Nanlin Hu; Jie Ju; Songlin Gao; Xiaobing Wang; Peng Yuan
• Keywords: Medicine (General); T-Lymphocytes; Ultrasonic Therapy; Apoptosis; Immunogenic Cell Death; Mammary Neoplasms, Animal; immune response; Mice; 03 medical and health sciences; breast cancer; R5-920; 0302 clinical medicine; International Journal of Nanomedicine; Cell Line, Tumor; immunogenic cell death; Animals; Original Research; Fluorocarbons; Mice, Inbred BALB C; Immunity; Dendritic Cells; Endocytosis; 3. Good health; dc maturation; Nanoparticles; Female; Immunotherapy; phase-transformation nanoparticles; T-Lymphocytes, Cytotoxic

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.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.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 B1, 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.The therapy of nanoparticles-mediated SDT can effectively enhance anti-tumor immune response of breast cancer.