Laboratory of Cellular and Molecular Cardiology, Cardiocentro Ticino Foundation, Lugano, Swiss Institute for Regenerative Medicine (SIRM), Taverne, Switzerland.
Laboratory of Cellular and Molecular Cardiology, Cardiocentro Ticino Foundation, Lugano, Swiss Institute for Regenerative Medicine (SIRM), Taverne, Switzerland; Dept. of Cardiology, University of Lausanne Medical Hospital (CHUV), Lausanne, Switzerland.
Pharmacol Ther. 2017 Jun;174:63-78. doi: 10.1016/j.pharmthera.2017.02.020. Epub 2017 Feb 12.
Virtually all cells in the organism secrete extracellular vesicles (EVs), a heterogeneous population of lipid bilayer membrane-enclosed vesicles that transport and deliver payloads of proteins and nucleic acids to recipient cells, thus playing central roles in cell-cell communications. Exosomes, nanosized EVs of endosomal origin, regulate many pathophysiological processes including immune responses and inflammation, tumour growth, and infection. Healthy subjects and patients with different diseases release exosomes with different RNA and protein contents into the circulation, which can be measured as biomarkers. The discovery of exosomes as natural carriers of functional small RNA and proteins has raised great interest in the drug delivery field, as it may be possible to harness these vesicles for therapeutic delivery of miRNA, siRNA, mRNA, lncRNA, peptides, and synthetic drugs. However, systemically delivered exosomes accumulate in liver, kidney, and spleen. Targeted exosomes can be obtained by displaying targeting molecules, such as peptides or antibody fragments recognizing target antigens, on the outer surface of exosomes. Display of glycosylphosphatidylinositol (GPI)-anchored nanobodies on EVs is a novel technique that enables EV display of a variety of proteins including antibodies, reporter proteins, and signaling molecules. However, naturally secreted exosomes show limited pharmaceutical acceptability. Engineered exosome mimetics that incorporate desirable components of natural exosomes into synthetic liposomes or nanoparticles, and are assembled using controllable procedures may be more acceptable pharmaceutically. In this communication, we review the current understanding of physiological and pathophysiological roles of exosomes, their potential applications as diagnostic markers, and current efforts to develop improved exosome-based drug delivery systems.
几乎所有的细胞都会分泌细胞外囊泡(EVs),这是一种异质的脂质双层膜包裹的囊泡群体,能够将蛋白质和核酸等有效载荷运输并递送到受体细胞,从而在细胞间通讯中发挥核心作用。外泌体是起源于内体的纳米级 EV,可调节多种病理生理过程,包括免疫反应和炎症、肿瘤生长和感染。健康个体和患有不同疾病的患者会将具有不同 RNA 和蛋白质含量的外泌体释放到循环中,这些外泌体可作为生物标志物进行测量。外泌体作为功能性小 RNA 和蛋白质的天然载体的发现,引起了人们对药物输送领域的极大兴趣,因为有可能利用这些囊泡来实现 miRNA、siRNA、mRNA、lncRNA、肽和合成药物的治疗性输送。然而,系统性递送的外泌体在肝脏、肾脏和脾脏中积累。通过在囊泡的外表面展示靶向分子,如识别靶抗原的肽或抗体片段,可以获得靶向的外泌体。在 EV 上展示糖基磷脂酰肌醇(GPI)锚定纳米抗体是一种新的技术,它使 EV 能够展示包括抗体、报告蛋白和信号分子在内的多种蛋白质。然而,天然分泌的外泌体的药物接受度有限。将天然外泌体的理想成分纳入合成脂质体或纳米颗粒中,并使用可控程序组装的工程外泌体模拟物可能在药物方面更具可接受性。在本通讯中,我们综述了对外泌体的生理和病理生理作用的现有理解,它们作为诊断标志物的潜在应用,以及目前开发改良的基于外泌体的药物输送系统的努力。
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