我们研究了负载顺铂 (CIS) 的脐带血 (UCB) 来源的 M1 巨噬细胞外泌体对卵巢癌和铂类耐药的治疗效果。使用 CD14 磁珠纯化 M1 巨噬细胞，并通过流式细胞术进行表征。我们的分析包括形态、粒径、颗粒浓度、电位、药物负载能力、进入细胞的计数、体内抗肿瘤作用以及逆转耐药性的能力。使用 CIS 或负载 CIS 的 M1 巨噬细胞外泌体 (M1exoCIS) 处理 A2780、SKOV3 和 A2780/DDP、SKOV3/DDP 卵巢癌细胞（分别为 CIS 敏感细胞系和 CIS 耐药细胞系）。 CIS 装载到 M1 巨噬细胞外泌体中的封装效率约为 30%。在体外，M1exoCIS 处理降低了 A2780、SKOV3 和 A2780/DDP、SKOV3/DDP 细胞的 CIS IC50 值。我们使用接种 A2780/DDP 细胞的小鼠卵巢癌皮下移植肿瘤模型评估了 M1exoCIS 对肿瘤生长的影响。治疗24小时后，在肝脏、脾脏和肿瘤部位观察到M1exoCIS； M1exoCIS的荧光强度高于CIS。 7天后，与单独的CIS相比，M1exoCIS显着抑制皮下移植肿瘤的生长，并且具有更长的生存时间。而且，毒性测试表明M1exoCIS的肝肾毒性比CIS小。为了研究 M1exoCIS 靶向、归巢和逆转耐药性的机制，我们进行了 RT-PCR、Western blotting 和 Proteome Profiler Human Receptor Array 分析。我们发现A2780和A2780/DDP细胞表达整合素β1/CD29受体，而M1外泌体表达整合素β1/CD29。此外，M1exos 携带长非编码 RNA H19，与 PTEN 蛋白上调以及 miR-130a 和 Pgp 基因下调有关，从而导致 CI​​S 耐药性的逆转。因此，UCB衍生的M1exoCIS靶向体内卵巢癌的肿瘤部位，可用于增加CIS的敏感性和细胞毒性。

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.