Sonosensitizer nanoplatform-mediated sonodynamic therapy induced immunogenic cell death and tumor immune microenvironment variation
作者全名："Zheng, Jing; Sun, Yixuan; Long, Tengfei; Yuan, Dong; Yue, Song; Zhang, Ni; Yang, Zhu"
作者地址："[Zheng, Jing; Sun, Yixuan; Long, Tengfei; Yuan, Dong; Yue, Song; Yang, Zhu] Chongqing Med Univ, Dept Gynecol & Obstet, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Zhang, Ni] Chongqing Med Univ, Dept Oncol, Affiliated Hosp 2, Chongqing 400010, Peoples R China"
通信作者："Yang, Z (通讯作者)，Chongqing Med Univ, Dept Gynecol & Obstet, Affiliated Hosp 2, Chongqing 400010, Peoples R China.; Zhang, N (通讯作者)，Chongqing Med Univ, Dept Oncol, Affiliated Hosp 2, Chongqing 400010, Peoples R China."
ESI学科分类：PHARMACOLOGY & TOXICOLOGY
关键词：Epithelial ovarian cancer; sonodynamic therapy; immunogenic cell death; ER stress; tumor microenvironment
摘要："Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic malignancies, and effective treatments are still lacking due to drug tolerance and tumor recurrence. In this study, we aimed to investigate the effects of sonodynamic therapy (SDT) on ovarian cancer and its potential mechanism. Folate receptor-targeted and ultrasound-responsive nanoparticles (NPs) were constructed using PLGA-PEG-FA (PLGA: poly (lactic-co-glycolic) acid, polyethylene glycol (PEG), FA: folate), the reactive oxygen species (ROS)-generating sonosensitizer IR780 and the oxygen-carrying material perfluorohexane (PFH), termed IRO@FA NPs. The antitumor effect of NPs triggered by ultrasound (US) was measured by an apoptosis assay in a C57/BL6 mouse model. Immunochemistry and flow cytometry were used to detect the proportion of CD3(+) T, CD4(+) T, CD8(+) T cells and activated dendritic cells (DCs) in spleens and tumor tissues to assess variation in the immune response. Moreover, endoplasmic reticulum (ER) stress and immunogenic cell death (ICD) markers (high mobility group protein box-1, ATP and calreticulin) were detected to identify potential mechanisms. The results showed that IRO@FA NP-mediated SDT promoted ID8 cell apoptosis both in vitro and in vivo. The densities of CD3(+) and CD8(+) T lymphocytes and inflammatory markers were upregulated in tumor tissues. IRO@FA NP-mediated SDT prompted DC maturation and T lymphocyte infiltration by inducing ID8 cell ICD."
基金机构："Chongqing Natural Science Foundation, China [cstc2021 jcyj-msxmX0402]; Science and Technology Research Project of Chongqing Education Commission, China [KJQN202000404]"
基金资助正文："This research was supported by Chongqing Natural Science Foundation, China cstc2021 jcyj-msxmX0402; Science and Technology Research Project of Chongqing Education Commission, China KJQN202000404."