We investigated the therapeutic efficacy of umbilical cord blood (UCB)-derived M1 macrophage exosomes loaded with cisplatin (CIS) in ovarian cancer and platinum resistance. M1 macrophages were purified by using CD14 magnetic beads and characterized by flow cytometry. Our analyses included morphology, particle size, particle concentration, potential, drug loading capacity, counts of entry into cells, antitumor effect in vivo, and the ability to reverse drug resistance. A2780, SKOV3, and A2780/DDP, SKOV3/DDP ovarian cancer cells (CIS-sensitive and CIS-resistant cell lines, respectively) were treated with CIS or CIS-loaded M1 macrophage exosomes (M1exoCISs). The encapsulation efficiency of CIS loading into M1 macrophage exosomes was approximately 30%. In vitro, M1exoCIS treatment reduced the CIS IC50 values of both A2780, SKOV3, and A2780/DDP, SKOV3/DDP cells. We evaluated the effect of M1exoCIS on tumor growth using a mouse ovarian cancer subcutaneous transplantation tumor model inoculated with A2780/DDP cells. M1exoCIS was observed in the liver, spleen, and tumor sites 24 h posttreatment; the fluorescence intensity of M1exoCIS is higher than that of CIS. After 7 days, M1exoCIS significantly inhibited the growth of subcutaneously transplanted tumors compared with CIS alone and had a longer survival time. Moreover, the toxicity test shows that M1exoCIS has less hepatorenal toxicity than CIS. To investigate the mechanism of M1exoCIS targeting, homing, and reversing drug resistance, we performed RT-PCR, Western blotting, and Proteome Profiler Human Receptor Array analyses. We found that A2780 and A2780/DDP cells expressed the integrin β1/CD29 receptor, while M1 exosomes expressed integrin β1/CD29. In addition, M1exos carries long noncoding RNA H19, implicated in PTEN protein upregulation and miR-130a and Pgp gene downregulation, leading to the reversal of CIS drug resistance. Therefore, UCB-derived M1exoCIS target tumor sites of ovarian cancer in vivo and can be used to increase the CIS sensitivity and cytotoxicity.Keywords: cisplatin; cord blood; drug resistance; exosome; macrophages; ovarian cancer.

---

 

乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
我们可提供从样本运输、储存管理、样本制备、样本检测到检测数据分析的全流程服务。凭借严格的实验室管理流程、标准化实验室操作、原始数据储存体系以及实验项目管理系统，已经为超过3000家客户单位提供服务，年检测样本超过100万，受到了广大客户的信任与支持。