Exosome mimetics: a novel class of drug delivery systems

Sander A A Kooijmans, Pieter Vader, Susan M van Dommelen, Wouter W van Solinge, Raymond M Schiffelers, Sander A A Kooijmans, Pieter Vader, Susan M van Dommelen, Wouter W van Solinge, Raymond M Schiffelers

Abstract

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.

Keywords: drug delivery systems; exosomes; extracellular vesicles; liposomes.

Figures

Figure 1
Figure 1
Schematic presentation of the biogenesis and composition of the three main classes of extracellular vesicles. Apoptotic bodies (left panel) are formed when cells enter apoptosis, and may contain nuclear material such as histones and DNA. They are heterogenous in size (50–5000 nm), irregularly shaped and harbor a variety of cellular proteins. Microvesicles (middle panel) are formed by budding and subsequent fission of the plasma membrane. Selective incorporation of membrane proteins and cytosolic proteins takes place during formation, resulting in vesicles which may be enriched in specific proteins and lipids compared to the parent cell. Microvesicles are thought to be smaller than apoptotic bodies (50–1000 nm) and more homogenously shaped. Selective enrichment of cellular content also occurs during the formation of exosomes (right panel), however exosomes originate from budding into the limiting membrane of large endosomal structures named multivesicular bodies (denoted with MVB). This process is facilitated by endosomal proteins. Subsequent fusion of MVBs with the plasma membrane results in release of the exosomes. Exosomes are small (Abbreviation: NC, nucleus.

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