Potential of peptide‐engineered exosomes with overexpressed miR‐92b‐3p in anti‐angiogenic therapy of ovarian cancer

作者：Jiaying Wang, Conghui Wang, Yang Li, Mingyue Li, Tingjia Zhu, Zhangjin Shen, Hui Wang, Weiguo Lv, Xinyu Wang, Xiaodong Cheng, Xing Xie · 发表于：Clinical and Translational Medicine · 年份：2021 · DOI：10.1002/ctm2.425 · 被引用次数：53 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、Ovarian cancer diagnosis and treatment

INTRODUCTION: Exosomal microRNA (miRNA) as a mediator of intercellular communication plays an essential part in tumor-relevant angiogenesis. Therapy against angiogenesis has been demonstrated to have a remarkable antitumor efficacy in various malignancies, but not as expected in ovarian cancer. METHODS: Exosomes were isolated by ultracentrifugation. Exosomal miRNA sequencing and gene function experiments were used to identify the differential expressed miRNAs in exosomes and their mRNA targets. SKOV3 cell line that stably overexpressed miR-92b-3p was constructed by lentivirus. In vitro, angiogenesis was analyzed by tube formation assay and migration assay. The angiogenic and antitumor effects in vivo were assessed in zebrafish and nude mouse models. Combination index was calculated to assess the synergetic inhibition of angiogenesis between miR-92b-3p and Apatinib. Peptides were conjugated with exosomal membranes to obtain engineered exosomes. RESULTS: Ovarian cancer cell-derived exosomes facilitated the angiogenesis and migration capability of vascular endothelial cells in vitro and in vivo. The expression of miR-92b-3p was much lower in ovarian cancer cell-derived exosomes than that in immortalized ovarian epithelial cell-derived exosomes. The exosomal miR-92b-3p modulated tumor-associated angiogenesis via targeting SOX4. Besides, Peptide-engineered exosomes with overexpressed miR-92b-3p showed the stronger abilities of anti-angiogenesis and antitumor than parental exosomes...