Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China.
Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China.
Int J Nanomedicine. 2021 Mar 5;16:1913-1926. doi: 10.2147/IJN.S297933. eCollection 2021.
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 CD4T, CD8T, CD8PD-1T 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. CD4T and CD8T cell subsets were significantly increased in blood, spleen and tumor tissue, meanwhile CD8PD-1T 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.
乳腺癌细胞的免疫静止已被认为是乳腺癌免疫治疗的主要障碍。在这项研究中，我们旨在研究纳米颗粒介导的声动力学疗法（SDT）在促进乳腺癌细胞抗肿瘤免疫中的作用及其潜在的免疫机制。
自行制备相转变纳米颗粒（LIP-PFH 纳米颗粒）并检测其理化性质。采用 CCK-8 检测、凋亡分析和 Balb/c 肿瘤模型建立，体外和体内研究低强度聚焦超声（LIFU）触发 LIP-PFH 纳米颗粒的抗肿瘤作用。流式细胞术和免疫组化检测血液、脾脏和肿瘤组织中 CD4T、CD8T、CD8PD-1T 的变化，以代表免疫反应的变化。检测免疫原性细胞死亡（ICD）标志物以研究潜在机制。
LIFU 触发的 LIP-PFH 纳米颗粒可抑制 4T1 细胞的增殖并促进其凋亡，无论是在体外还是体内。血液、脾脏和肿瘤组织中 CD4T 和 CD8T 细胞亚群明显增加，同时 CD8PD-1T 细胞减少，表明纳米颗粒介导的 SDT 增强了乳腺癌细胞的抗肿瘤免疫反应。ICD 标志物（ATP、高迁移率族蛋白 B1 和钙网蛋白）的检测和树突状细胞（DC）成熟的流式细胞分析进一步表明，纳米颗粒介导的 SDT 通过诱导乳腺癌细胞的 ICD 可促进 DC 成熟，增加细胞毒性 T 细胞的比例。
纳米颗粒介导的 SDT 治疗可有效增强乳腺癌的抗肿瘤免疫反应。
