Combined treatment with a pH-sensitive fusogenic peptide and cationic lipids achieves enhanced cytosolic delivery of exosomes.
Combined treatment with a pH-sensitive fusogenic peptide and cationic lipids achieves enhanced cytosolic delivery of exosomes.
复制标题
DOI：
10.1038/srep10112
复制
发表时间：
2015-05-26
影响因子：
4.6
通讯作者：
Futaki S
中科院分区：
文献类型：
--
作者：
Nakase I;Futaki S
外泌体是由细胞分泌的约100 nm的囊泡，已经就细胞间通讯、疾病诊断和细胞内递送进行了研究。外泌体的细胞摄取通过内吞作用发生;然而，细胞内包封的分子的胞质释放效率低。为了解决这个问题，在这里，我们展示了一种简单的技术，通过结合pH敏感的融合肽，用于融合细胞内的内体和外泌体膜，来增强细胞摄取和外泌体的胞质释放。该方法用阳离子脂质刺激外泌体内容物的有效胞质释放，阳离子脂质充当“胶”以支持细胞摄取。使用这种简单的组合技术，实现了外泌体中人工包封的葡聚糖大分子（70 kDa）的有效细胞摄取和胞质释放，并且用人工包封的核糖体失活蛋白皂草素实现了生物活性的显著改善。我们的方法将有助于许多生物学研究领域，包括评估外泌体内容物的活性，以及开发候选工具，使细胞内可视化和细胞调控成为未来的治疗应用。
Exosomes, which are approximately 100 nm vesicles secreted by cells, have been studied with respect to cell-to-cell communication, disease diagnosis, and intracellular delivery. The cellular uptake of exosomes occurs by endocytosis; however, the cytosolic release efficiency of encapsulated molecules inside cells is low. To address this issue, here we demonstrate a simple technique for enhancing the cellular uptake and cytosolic release of exosomes by combining a pH-sensitive fusogenic peptide for the fusion of endosomal and exosomal membranes inside cells. This method stimulates the efficient cytosolic release of the exosomal contents with cationic lipids that act as a “glue” to support cellular uptake. Using this simple combined technique, the effective cellular uptake and cytosolic release of an artificially encapsulated dextran macromolecule (70 kDa) in exosomes are achieved, and a marked improvement in bioactivity is attained with the artificially encapsulated ribosome-inactivating protein saporin. Our method will contribute to many biological research fields, including the assessment of the activities of exosomal contents and the development of candidate tools enabling intracellular visualisation and cellular regulation for future therapeutic applications.
登录
查看更多内容
影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
影响因子：
3.7
作者：
Ogata-Kawata H;Izumiya M;Kurioka D;Honma Y;Yamada Y;Furuta K;Gunji T;Ohta H;Okamoto H;Sonoda H;Watanabe M;Nakagama H;Yokota J;Kohno T;Tsuchiya N
通讯作者：
Tsuchiya N
影响因子：
3.5
作者：
Futaki, S;Masui, Y;Harashima, H
通讯作者：
Harashima, H
影响因子：
5.8
作者：
Sokolova, Viktoriya;Ludwig, Anna-Kristin;Glebel, Bernd
通讯作者：
Glebel, Bernd
影响因子：
4.7
作者：
Kobayashi, Sachiko;Nakase, Ikuhiko;Futaki, Shiroh
通讯作者：
Futaki, Shiroh