Development of novel cancer therapy using miRNA containing exosome

尽管核酸药物具有治疗潜力，但它们的临床应用在一定程度上受到缺乏适当给药系统的限制。外体或微囊是由各种细胞类型和组织分泌的小的内胚体来源的囊泡。在这里，我们展示了外切体可以有效地将microRNA运送到表达表皮生长因子受体(EGFR)的乳腺癌细胞。靶向性是通过改造供体细胞来表达融合到Ge11肽上的血小板衍生生长因子受体的跨膜区。静脉注射Exosome将let-7a microRNA传递到表达EGFR的Rag2-/-小鼠的异种乳腺癌组织。此外，我们还开发了具有高效负载RISC复合体活性的模拟miRNA。我们的结果表明，外切体可以用来通过核酸药物来靶向表达EGFR的癌症组织。

Despite the therapeutic potential of nucleic acid drugs, their clinical application has been limited in part by a lack of appropriate delivery systems. Exosomes or microvesicles are small endosomally derived vesicles that are secreted by a variety of cell types and tissues. Here, we show that exosomes can efficiently deliver microRNA to epidermal growth factor receptor (EGFR)-expressing breast cancer cells. Targeting was achieved by engineering the donor cells to express the transmembrane domain of platelet-derived growth factor receptor fused to the GE11 peptide. Intravenously injected exosomes delivered let-7a microRNA to EGFR-expressing xenograft breast cancer tissue in Rag2-/- mice. Furthermore, we developed mimic miRNA that have efficient loading activity of the RISC complex. Our results suggest that exosomes can be used therapeutically to target EGFR-expressing cancerous tissues with nucleic acid drugs.