Department of Biological Chemistry, Graduate School of Science, Osaka Metropolitan University, 1-1, Gakuen-cho, Naka-ku, Sakai 599-8531, Osaka, Japan.
Department of Applied Chemistry, Graduate School of Engineering, Osaka Metropolitan University, 1-1 Gakuen-cho, Naka-ku, Sakai 599-8531, Osaka, Japan.
ACS Appl Mater Interfaces. 2024 Apr 10;16(14):17069-17079. doi: 10.1021/acsami.3c14592. Epub 2024 Apr 2.
Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), transfer bioactive molecules from donor to recipient cells in various pathophysiological settings, thereby mediating intercellular communication. Despite their significant roles in extracellular signaling, the cellular uptake mechanisms of different EV subpopulations remain unknown. In particular, plasma membrane-derived MVs are larger vesicles (100 nm to 1 μm in diameter) and may serve as efficient molecular delivery systems due to their large capacity; however, because of size limitations, receptor-mediated endocytosis is considered an inefficient means for cellular MV uptake. This study demonstrated that macropinocytosis (lamellipodia formation and plasma membrane ruffling, causing the engulfment of large fluid volumes outside cells) can enhance cellular MV uptake. We developed experimental techniques to induce macropinocytosis-mediated MV uptake by modifying MV membranes with arginine-rich cell-penetrating peptides for the intracellular delivery of therapeutic molecules.
细胞外囊泡（EVs），包括外泌体和微泡（MVs），可以在各种病理生理条件下将生物活性分子从供体细胞转移到受体细胞，从而介导细胞间通讯。尽管它们在细胞外信号转导中具有重要作用，但不同 EV 亚群的细胞摄取机制仍不清楚。特别是，源自质膜的 MV 是较大的囊泡（直径 100nm 至 1μm），由于其容量较大，可能成为有效的分子递药系统；然而，由于尺寸限制，受体介导的内吞作用被认为是细胞摄取 MV 的低效方式。本研究表明，巨胞饮（形成片状伪足和质膜皱襞，导致细胞外大量液体的摄取）可以增强细胞摄取 MV。我们通过用富含精氨酸的细胞穿透肽修饰 MV 膜来开发实验技术，以诱导巨胞饮介导的 MV 摄取，从而实现治疗分子的细胞内递药。
