Focus on Extracellular Vesicles: Development of Extracellular Vesicle-Based Therapeutic Systems

Abstract

Many types of cells release phospholipid membrane vesicles thought to play key roles in cell-cell communication, antigen presentation, and the spread of infectious agents. Extracellular vesicles (EVs) carry various proteins, messenger RNAs (mRNAs), and microRNAs (miRNAs), like a "message in a bottle" to cells in remote locations. The encapsulated molecules are protected from multiple types of degradative enzymes in body fluids, making EVs ideal for delivering drugs. This review presents an overview of the potential roles of EVs as natural drugs and novel drug-delivery systems.

Keywords: clinical trial; dexosome; drug delivery system; exosome; extracellular vesicle; microvesicle; outer membrane vesicle; stem cell; vaccine.

Figure 1

Research aimed at developing extracellular vesicles (EVs) for clinical applications. APC: Antigen presenting cell; DCs: Dendritic cells; iDCs: Immature dendritic cells; DDS: Drug delivery system; GVHD: Graft-versus-host disease; MSCs: Mesenchymal stem cells.

Figure 2

Comparison of liposomes and extracellular vesicles (EVs) as drug-delivery-systems (DDS). (A) Schematic depiction of lipid-based vesicular carriers (not to scale). Note that in comparison to liposomes, EV membranes not only consist of a diverse number of lipid classes, but also contain trans-membrane and membrane-associated proteins, receptors, adhesion molecules, as well as a natural corona. Such features must be engineered into liposomes to obtain a stable and suitable DDS; (B) Accumulation of exosomes is profoundly higher (B₂) than accumulation of artificial nano-carriers such as liposomes (B₁; white arrows) in PC12 neuronal cells after 24 h incubation [12]. Red (Dil, C₅₉H₉₇ClN₂O₄): exosomes or nano-carriers; Green (rabbit anti-PGP9.5): actin microfilaments; Blue (DAPI): nuclei.