Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
Life Sci. 2021 Feb 1;266:118871. doi: 10.1016/j.lfs.2020.118871. Epub 2020 Dec 9.
Exosomes hold great promise as bio-inspired delivery vehicles. Mesenchymal stem cells (MSCs) are recognized for their potential to yield huge quantities of exosomes. We aimed to investigate the potential use of modified exosomes derived from genetically modified dental pulp MSCs (DPSCs) as a carrier to deliver tumor suppressor miR-34a to repress proliferation of breast carcinoma cells.
miR-34a-overexpressing DPSCs were prepared using XMIRXpress-34a lentivectors. The anticancer effects of the miR-34a-loaded exosomes were evaluated on breast carcinoma cells through apoptosis, migration, and invasion assays. Given the structural similarity between exosomes and liposomes, we compared the exosome-mediated miRNA delivery efficiency with that of liposomes.
Our data demonstrated that genetically modified DPSCs were capable of secretion of exosomes enriched with therapeutic miRNAs and presented the feasibility of application of exosome-based vehicle for gene delivery.
We showed the potential of MSC-derived exosomes as a tool for delivery of miRNAs in vitro. Nevertheless, optimizing gene-loading approaches is required before exosomes can be intended as a miRNA carrier for therapeutic applications.
外泌体作为仿生递药载体具有巨大的应用潜力。间充质干细胞（MSCs）因其能够大量产生外泌体而备受关注。本研究旨在探讨来源于基因修饰牙髓间充质干细胞（DPSCs）的修饰外泌体作为载体，递送肿瘤抑制因子 miR-34a 以抑制乳腺癌细胞增殖的潜在用途。
利用 XMIRXpress-34a 慢病毒载体制备 miR-34a 过表达的 DPSCs。通过细胞凋亡、迁移和侵袭实验评估载有 miR-34a 的外泌体对乳腺癌细胞的抗癌作用。鉴于外泌体和脂质体之间的结构相似性，我们比较了外泌体介导的 miRNA 递释效率与脂质体的效率。
我们的数据表明，基因修饰的 DPSCs 能够分泌富含治疗性 miRNA 的外泌体，并证明了基于外泌体的载体在基因传递中的应用可行性。
我们展示了 MSC 衍生的外泌体作为体外递送 miRNA 的工具的潜力。然而，在将外泌体用作治疗性 miRNA 载体之前，需要优化基因加载方法。
