Exosome mimetics: a novel class of drug delivery systems.
Exosome mimetics: a novel class of drug delivery systems.
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DOI：
10.2147/ijn.s29661
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发表时间：
2012
影响因子：
8
通讯作者：
Schiffelers RM
中科院分区：
文献类型：
--
作者：
Kooijmans SA;Vader P;van Dommelen SM;van Solinge WW;Schiffelers RM
细胞外磷脂囊泡作为细胞信息传递载体的发现在药物传递领域引起了人们的兴奋。生物治疗剂，包括短干扰RNA和重组蛋白，易于降解，具有有限的穿过生物膜的能力，并且可能引发免疫应答。因此，正在对这类药物的输送系统进行深入研究。利用细胞外囊泡作为生物治疗剂的载体是克服这些问题并实现有效递送至靶细胞胞质溶胶的有希望的策略。外泌体是一类被充分研究的细胞外囊泡，已知其携带蛋白质和核酸，使其特别适合于此类策略。然而，这些载体的相当大的复杂性和相关的高脱靶效应机会是转化为临床的主要障碍。考虑到并非外泌体的所有组分都是其正常功能所需的，一种替代策略将是合成模拟这些囊泡。通过组装仅含有天然外泌体的关键组分的脂质体，可以产生功能性外泌体模拟物。低复杂性和良好表征的组分的使用强烈地增加了此类系统的药学可接受性。然而，组装功能性外泌体模拟物所需的外泌体组分仍有待鉴定。本文综述了外泌体的组成和功能特性，并重点介绍了可用于增强外泌体模拟物药物递送特性的组分。
The identification of extracellular phospholipid vesicles as conveyors of cellular information has created excitement in the field of drug delivery. Biological therapeutics, including short interfering RNA and recombinant proteins, are prone to degradation, have limited ability to cross biological membranes, and may elicit immune responses. Therefore, delivery systems for such drugs are under intensive investigation. Exploiting extracellular vesicles as carriers for biological therapeutics is a promising strategy to overcome these issues and to achieve efficient delivery to the cytosol of target cells. Exosomes are a well studied class of extracellular vesicles known to carry proteins and nucleic acids, making them especially suitable for such strategies. However, the considerable complexity and the related high chance of off-target effects of these carriers are major barriers for translation to the clinic. Given that it is well possible that not all components of exosomes are required for their proper functioning, an alternative strategy would be to mimic these vesicles synthetically. By assembly of liposomes harboring only crucial components of natural exosomes, functional exosome mimetics may be created. The low complexity and use of well characterized components strongly increase the pharmaceutical acceptability of such systems. However, exosomal components that would be required for the assembly of functional exosome mimetics remain to be identified. This review provides insights into the composition and functional properties of exosomes, and focuses on components which could be used to enhance the drug delivery properties of exosome mimetics.