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Proteomics. 2019 Feb 20:e1800161. doi: 10.1002/pmic.201800161. [Epub ahead of print]

Exosome-mimetic nanovesicles contain distinct proteome and post-translational modified protein cargo, in comparison to exosomes.

Author information

1
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Australia.
2
Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Denmark.

Abstract

Cargo sorting of selective biomolecules and relatively low quantities of extracellular vesicles (EVs) produced by cells present challenges when upscaling EV production for therapeutic use. These issues may be overcome through producing artificial EVs. Cell-derived mimetic nanovesicles (M-NVs) are a potentially promising alternative to EVs for clinical applicability, demonstrating cost-effectiveness and higher yield without incumbent production and isolation issues. Although several studies have shown that M-NVs have similar morphology, size and therapeutic potential compared to exosomes, comprehensive characterization and to what extent M-NVs components mimic exosomes remain elusive. We generated M-NVs through the extrusion of cells and performed proteomic profiling which defined proteins associated with membrane and cytosolic components. In this context, our proteomic data reveal a subset of proteins that are highly abundant in M-NVs in comparison to exosomes. M-NVs contain proteins that largely represent the parental cell proteome, whereas the profile of exosomal proteins highlight their endosomally derived origin. This advantage of M-NVs alleviates the necessity of endosomal sorting of endogenous therapeutic proteins or RNA into exosomes. Our study also highlights differences in protein post-translational modifications among M-NVs, as distinct from exosomes, using a non-targeted informatic approach, specifically showing phosphorylation, ubiquitination, and thiophosphorylation as enriched protein modifications in M-NVs. Overall this study provides key insights into defining the proteome composition of M-NVs as a distinct from exosomes, and the potential advantage of M-NVs as an alternative nanocarrier when spontaneous endosomal sorting of therapeutics are limited. This article is protected by copyright. All rights reserved.

KEYWORDS:

artificial extracellular vesicles; exosomes; extracellular vesicles; mimetic-nanovesicles; post-translational modification; proteomics; therapeutic exosomes

PMID:
30790448
DOI:
10.1002/pmic.201800161

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