Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai, China.
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Drug Dev Ind Pharm. 2020 Jul;46(7):1150-1162. doi: 10.1080/03639045.2020.1776320. Epub 2020 Jun 16.
To assess the feasibility of an exosome-based drug delivery platform for the potent chemotherapeutic agent cisplatin to treat ovarian cancer. Exosomes have recently been used as drug delivery vehicles because of their natural advantages. Platinum-resistant forms of ovarian cancer require novel drug delivery methods to improve patient outcomes. We developed and compared different methods of loading exosomes released by mononuclear M1 and M2 macrophages from umbilical cord blood with cisplatin. We characterized the morphology, drug capacity, method of cellular entry, and antitumor efficacy of the exosomes . Disruption of the exosomal membrane by sonication facilitated a high loading efficiency. Importantly, incorporation of cisplatin into umbilical cord blood-derived M1 macrophage exosomes increased its cytotoxicity 3.3× in drug-resistant A2780/DDP cells and 1.4× in drug-sensitive A2780 cells over chemotherapy alone. Loading of cisplatin into M2 exosomes increased its cytotoxicity by nearly 1.7× in drug-resistant A2780/DDP cells and 1.4× in drug-sensitive A2780 cells. We conclude that cisplatin-loaded M1 exosomes are potentially powerful new tools for the delivery of chemotherapeutics to treat cancers regardless of drug resistance.
为了评估基于外泌体的药物传递平台用于治疗卵巢癌的有效化疗药物顺铂的可行性。由于其天然优势，外泌体最近被用作药物传递载体。需要新的药物传递方法来改善铂耐药型卵巢癌患者的预后。我们开发并比较了用单核 M1 和 M2 巨噬细胞从脐血中释放的外泌体加载顺铂的不同方法。我们对其形态、载药量、细胞进入方式和抗肿瘤功效进行了表征。超声处理破坏外泌体膜可实现高载药效率。重要的是，将顺铂掺入源自 M1 巨噬细胞的脐血外泌体中，可使耐药 A2780/DDP 细胞中的细胞毒性增加 3.3 倍，而使敏感 A2780 细胞中的细胞毒性增加 1.4 倍，与单独化疗相比。将顺铂加载到 M2 外泌体中，可使耐药 A2780/DDP 细胞中的细胞毒性增加近 1.7 倍，使敏感 A2780 细胞中的细胞毒性增加 1.4 倍。我们得出结论，载顺铂的 M1 外泌体是治疗癌症的新的有效化疗药物的有力传递工具，而与耐药性无关。
