Extracellular vesicle mimetics: novel alternatives to extracellular vesicle-based theranostics, drug delivery, and vaccines

Extracellular vesicles are nano-sized spherical bilayered proteolipids encasing various components. Cells of all domains of life actively release these vesicles to the surroundings including various biological fluids. These extracellular vesicles are known to play pivotal roles in numerous pathophysiological functions. Extracellular vesicles have distinct characteristics, like high biocompatibility, safety, and nano-sized diameters that allow efficient drug loading capacity and long blood circulation half-life. These characteristics of extracellular vesicles have engrossed many scientists to harness them as new tools for novel delivery systems.

Here, researchers from Pohang University of Science and Technology discuss the current state of the arts and problems of such extracellular vesicle-based theranostics, drug delivery and vaccines, and introduce “extracellular vesicle mimetics” as the novel alternative of extracellular vesicles. They provide insights into the potential of extracellular vesicle mimetics as superior substitute to the natural extracellular vesicles that can be applied to theranostics, drug delivery, and vaccines against various diseases.

Generation of bacterial extracellular vesicle-mimetic nanovesicles

Bacterial cells or genetically engineered bacterial cells (either with luminal or membrane proteins) are suspended in Tris buffer with EDTA and lysozyme to remove the outer membrane and cell wall to form bacterial protoplasts. The bacterial protoplasts are serially extruded with 10, 5, and 1 μm pore-sized membrane filters to form nanovesicles. Then, the nanovesicles are isolated by two-step density gradient ultracentrifugation.