Abstract

Exosomes are a valuable biomaterial for the development of novel nanocarriers as functionally advanced drug delivery systems. To control and modify the performance of exosomal nanocarriers, we developed hybrid exosomes by fusing their membranes with liposomes using the freeze–thaw method. Exosomes embedded with a specific membrane protein isolated from genetically modified cells were fused with various liposomes, confirming that membrane engineering methods can be combined with genetic modification techniques. Cellular uptake studies performed using the hybrid exosomes revealed that the interactions between the developed exosomes and cells could be modified by changing the lipid composition or the properties of the exogenous lipids. These results suggest that the membrane-engineering approach reported here offers a new strategy for developing rationally designed exosomes as hybrid nanocarriers for use in advanced drug delivery systems.

Highlights

  • Exosomes are a valuable biomaterial for the development of novel nanocarriers as functionally advanced drug delivery systems

  • Labelled liposomes were prepared by extruding an aqueous liposome dispersion comprising 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC; zwitterionic), 1,2-dioleoyl-sn-glycero3-phospho-l-serine; (DOPS, anionic), 1,2-dioleoyl-3-trimethylammonium propane (DOTAP; cationic) or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N–[methoxy(polyethylene glycol)-2000] (PEG-DSPE; Mw 2000 poly(ethylene glycol) (PEG) was introduced to lipid head) in the presence of fluorescently-lebelled lipids, 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-(lissamine rhodamine B sulfonyl) or 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) (NBD-DMPE)

  • We developed engineered hybrid exosomes by fusing the membranes of exosomes with liposomes using the freeze–thaw method

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Summary

Introduction

Exosomes are a valuable biomaterial for the development of novel nanocarriers as functionally advanced drug delivery systems. Cellular uptake studies performed using the hybrid exosomes revealed that the interactions between the developed exosomes and cells could be modified by changing the lipid composition or the properties of the exogenous lipids. These results suggest that the membraneengineering approach reported here offers a new strategy for developing rationally designed exosomes as hybrid nanocarriers for use in advanced drug delivery systems. Exosomes can be loaded with a diverse range of biological molecules, including cytosolic proteins, membrane receptors, and nucleic acids Because of these delivery functions, the exosomes have been investigated to use as novel nanocarriers for advanced drug delivery systems. Such techniques may have adverse effects on the exosomes and cargoes, by promoting aggregation for example[19]

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