Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Life Sci. 2020 Nov 15;261:118369. doi: 10.1016/j.lfs.2020.118369. Epub 2020 Aug 31.
Exosomes hold great potential for cancer treatment to deliver therapeutics due to its inherent low immunogenicity. Exosomes are biocompatible cell-exocytosed secreted vesicles by most cell types, which can be used to construct novel biomanufacturing platform for drug delivery and cancer therapy. In this study, we implemented nano-sized vesicles which were secreted by mesenchymal stem cell (MSC), to encapsulate doxorubicin (DOX) through electroporation method (DOX@exosome). DOX was loaded into exosomes, with an encapsulation efficiency of up to 35% and separated by ultracentrifugation. Subsequently, carboxylic acid-end MUC1 aptamer was used to covalently decorate the surface amine groups of the exosomes via amide bond formation to provide selective guided drug delivery (DOX@exosome-apt). The data showed that the DOX@exosome-apt provided highly efficient DOX transportation to MUC1-positive cancer cells in vitro as confirmed by MTT and flow cytometry experiments. Moreover, in vivo study on ectopic model of C26 (mouse colon adenocarcinoma) in BALB/c mice indicated that the single dose intravenous injection of DOX@exosome-apt significantly suppress tumor growth in comparison with free DOX. Ex vivo fluorescent imaging also verified the desirable biodistribution of DOX@exosome-apt by exhibiting higher tumor accumulation and faster liver clearance in comparison with DOX@exosome and free DOX. It could be concluded that MUC1 aptamer-decorated exosomes can be implemented therapeutically for the safe and versatile delivery of DOX to colon adenocarcinoma, thus offering valuable platform for clinical applications.
外泌体由于其固有低免疫原性，在癌症治疗中具有很大的治疗潜力，可用于传递治疗药物。外泌体是大多数细胞类型通过细胞外排分泌的生物相容性细胞外囊泡，可用于构建新型生物制造平台，用于药物输送和癌症治疗。在这项研究中，我们通过电穿孔法（DOX@exosome）实施了由间充质干细胞（MSC）分泌的纳米大小的囊泡，以封装阿霉素（DOX）。DOX 被装载到外泌体中，包封效率高达 35%，并通过超速离心分离。随后，通过酰胺键形成，使用羧酸末端 MUC1 适体共价修饰外泌体的表面胺基，以提供选择性引导药物输送（DOX@exosome-apt）。数据表明，DOX@exosome-apt 为体外 MUC1 阳性癌细胞提供了高效的 DOX 转运，这一点通过 MTT 和流式细胞术实验得到了证实。此外，在 BALB/c 小鼠的 C26（小鼠结肠腺癌）异位模型中的体内研究表明，与游离 DOX 相比，单次静脉注射 DOX@exosome-apt 可显著抑制肿瘤生长。离体荧光成像也证实了 DOX@exosome-apt 的理想生物分布，与 DOX@exosome 和游离 DOX 相比，其在肿瘤中的积累更高，在肝脏中的清除更快。可以得出结论，MUC1 适体修饰的外泌体可用于安全且多功能地将 DOX 递送到结肠腺癌，从而为临床应用提供有价值的平台。
