Nanoscience and Nanotechnology Research Center, Research Organization for the 21st Century, Osaka Prefecture University, 1-2, Gakuen-cho, Naka-ku, Sakai, Osaka, 599-8570, Japan.
Graduate School of Science, Osaka Prefecture University, 1-1, Gakuen-cho, Naka-ku, Sakai, Osaka, 599-8531, Japan.
Sci Rep. 2017 May 16;7(1):1991. doi: 10.1038/s41598-017-02014-6.
Extracellular vesicles (EVs) including exosomes have been shown to play crucial roles in cell-to-cell communication because of their ability to carry biofunctional molecules (e.g., microRNAs and enzymes). EVs also have pharmaceutical advantages and are highly anticipated to be a next-generation intracellular delivery tool. Here, we demonstrate an experimental technique that uses arginine-rich cell-penetrating peptide (CPP)-modified EVs to induce active macropinocytosis for effective cellular EV uptake. Modification of arginine-rich CPPs on the EV membrane resulted in the activation of the macropinocytosis pathway, and the number of arginine residues in the peptide sequences affected the cellular EV uptake efficiency. Consequently, the ribosome-inactivating protein saporin-encapsulated EVs modified with hexadeca-arginine (R16) peptide effectively attained anti-cancer activity.
细胞外囊泡（EVs）包括外泌体，由于其能够携带生物功能分子（例如 microRNAs 和酶），因此在细胞间通讯中发挥着至关重要的作用。EVs 还具有药物优势，有望成为下一代细胞内递药工具。在这里，我们展示了一种实验技术，该技术使用富含精氨酸的细胞穿透肽（CPP）修饰的 EVs 诱导主动巨胞饮作用，从而有效摄取细胞 EV。在 EV 膜上修饰富含精氨酸的 CPP 会导致巨胞饮途径的激活，并且肽序列中的精氨酸残基数量会影响细胞摄取 EV 的效率。因此，用十六精氨酸（R16）肽修饰的含有核糖体失活蛋白 saporin 的 EVs 有效地获得了抗癌活性。
