Engineering exosomes as refined biological nanoplatforms for drug delivery

Abstract

Exosomes, a subgroup of extracellular vesicles (EVs), have been recognized as important mediators of long distance intercellular communication and are involved in a diverse range of biological processes. Because of their ideal native structure and characteristics, exosomes are promising nanocarriers for clinical use. Exosomes are engineered at the cellular level under natural conditions, but successful exosome modification requires further exploration. The focus of this paper is to summarize passive and active loading approaches, as well as specific exosome modifications and examples of the delivery of therapeutic and imaging molecules. Examples of exosomes derived from a variety of biological origins are also provided. The biocompatible characteristics of exosomes, with suitable modifications, can increase the stability and efficacy of imaging probes and therapeutics while enhancing cellular uptake. Challenges in clinical translation of exosome-based platforms from different cell sources and the advantages of each are also reviewed and discussed.

Figure 1

Exosome generation, secretion and cargo transfer from the donor cells to the recipient cells. Exosome are small membrane vesicles secreted by most cell types. Internal vesicles form by the inward budding of the cellular compartments known as multivesicular body (MVB). When MVB fuse with the plasma membrane, these internal vesicles are released as exosomes, which can transfer the DNA, RNA and proteins to the distant recipient cells, and influent various aspects of cell behavior and physiology. The inset shows a typical ultracentrifugation protocol. In consecutive rounds of centrifugation and pouring off, the RCF (g) and the centrifugation time are increased to pellet smaller particles. After first 200×g and 2000×g centrifugations, pellets that contain dead cells and cell debris are discarded, and the supernatant is kept for the next step. In contrast, after the 100 000×g centrifugations, pellets (containing EVs) are kept, and supernatants are discarded. The pellets are resuspended in phosphate buffered saline (PBS) for further analysis.

Figure 2

Schematic representation of the different types of exosomes drug delivery systems. Exosomes consist of a lipid bilayer that can be composed of lipids, which encloses an aqueous core. Both the lipid bilayer and the aqueous space can incorporate hydrophobic (A) or hydrophilic compounds (B), respectively. (C) Exosomes can be used for DNA, RNA and protein delivery. (D) Theranostic or imaging probes, specific targeting ligands and covalent linkage can be attached to exosome surface.