Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

Abstract

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are nanosized membrane vesicles derived from most cell types. Carrying diverse biomolecules from their parent cells, EVs are important mediators of intercellular communication and thus play significant roles in physiological and pathological processes. Owing to their natural biogenesis process, EVs are generated with high biocompatibility, enhanced stability, and limited immunogenicity, which provide multiple advantages as drug delivery systems (DDSs) over traditional synthetic delivery vehicles. EVs have been reported to be used for the delivery of siRNAs, miRNAs, protein, small molecule drugs, nanoparticles, and CRISPR/Cas9 in the treatment of various diseases. As a natural drug delivery vectors, EVs can penetrate into the tissues and be bioengineered to enhance the targetability. Although EVs' characteristics make them ideal for drug delivery, EV-based drug delivery remains challenging, due to lack of standardized isolation and purification methods, limited drug loading efficiency, and insufficient clinical grade production. In this review, we summarized the current knowledge on the application of EVs as DDS from the perspective of different cell origin and weighted the advantages and bottlenecks of EV-based DDS.

Keywords: Drug delivery; exosomes; extracellular vesicles; microvesicles.

Figure 1.

Scheme of biogenesis of three types of extracellular vesicles (exosomes, microvesicles, and apoptotic bodies) and component of exosome. Exosomes are cell secreted vesicles of ∼100 nm in size and packed with a variety of cellular components including mRNAs, miRNAs, proteins, enzymes, lipids, carbohydrates, etc. The exosome surface is decorated with various membrane proteins responsible for different pathophysiological functions.

Figure 2.

Scheme of the potential of EVs in disease treatment and drug delivery. EVs can be isolated from different ‘factories’ (dendritic cells, mesenchymal stem cells, macrophages, milk, tumor cells, others), loading different cargos (small molecules, nucleic acids, protein, metal nanoparticles), and targeting to precise disease (cardiovascular disease, neurodegenerative disease, osteoporosis, cancer, malignancies, and metastasis).