ABSTRACT
Recent studies clearly show that cell-derived extracellular vesicles (EVs, including exosomes) can promote hair growth. However, large-scale production of EVs remains a big hurdle. Recently, extracellular vesicle mimetics (EMs) engineered by extrusion through various membranes are emerging as a complementary approach for large-scale production. In this study, to investigate their ability to induce hair growth, we generated macrophage-engineered EMs (MAC-EMs) that activated the human dermal papilla (DP) cells in vitro. MAC-EMs intradermally injected into the skin of C57BL/6 mice were retained for up to 72 h. Microscopy imaging revealed that MAC-EMs were predominately internalized into hair follicles. The MAC-EMs treatment induced hair regrowth in mice and hair shaft elongation in a human hair follicle, suggesting the potential of MAC-EMs as an alternative to EVs to overcome clinical limitation.
Subject(s)
Extracellular Vesicles/metabolism , Hair Follicle/growth & development , Hair Follicle/metabolism , Hair/metabolism , Macrophages/metabolism , Animals , Cell Proliferation/physiology , Cells, Cultured , Dermis/growth & development , Dermis/metabolism , Dermis/physiology , Exosomes/metabolism , Hair/growth & development , Humans , Macrophages/physiology , Male , Mice , Mice, Inbred C57BL , RAW 264.7 Cells , Skin/metabolism , Wnt Signaling Pathway/physiologyABSTRACT
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. This review will highlight 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. We hope to 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.
Subject(s)
Drug Delivery Systems/methods , Extracellular Vesicles/chemistry , Meningitis, Bacterial/prevention & control , Sepsis/prevention & control , Theranostic Nanomedicine/methods , Animals , Biomimetic Materials/administration & dosage , Biomimetic Materials/chemistry , Biomimetic Materials/metabolism , Drug Compounding/methods , Escherichia coli/chemistry , Extracellular Vesicles/immunology , Humans , Meningitis, Bacterial/immunology , Meningitis, Bacterial/microbiology , Nanostructures/administration & dosage , Nanostructures/chemistry , Neisseria meningitidis/chemistry , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Sepsis/immunology , Sepsis/microbiology , Vaccination , Vaccines/administration & dosage , Vaccines/chemistryABSTRACT
The maintenance of a high delivery efficiency by traditional nanomedicines during cancer treatment is a challenging task. As a natural mediator for short-distance intercellular communication, extracellular vesicles (EVs) have garnered significant attention owing to their low immunogenicity and high targeting ability. They can load a variety of major drugs, thus offering immense potential. In order to overcome the limitations of EVs and establish them as an ideal drug delivery system, polymer-engineered extracellular vesicle mimics (EVMs) have been developed and applied in cancer therapy. In this review, we discuss the current status of polymer-based extracellular vesicle mimics in drug delivery, and analyze their structural and functional properties based on the design of an ideal drug carrier. We anticipate that this review will facilitate a deeper understanding of the extracellular vesicular mimetic drug delivery system, and stimulate the progress and advancement of this field.
ABSTRACT
Extracellular vesicles (EVs) have attracted attention as delivery vehicles due to their structure, composition, and unique properties in regeneration and immunomodulation. However, difficulties during production and isolation processes of EVs limit their large-scale clinical applications. EV mimetics (EVMs), prepared via top-down strategies that improve the yield of nanoparticles while retaining biological properties similar to those of EVs have been used to address these limitations. Herein, the preparation of EVMs is reviewed and their characteristics in terms of structure, composition, targeting ability, cellular uptake mechanism, and immunogenicity, as well as their strengths, limitations, and future clinical application prospects as EV alternatives are summarized.
Subject(s)
Extracellular Vesicles , Nanoparticles , Biological Transport , Excipients , Extracellular Vesicles/chemistryABSTRACT
Extracellular vesicles (EVs) are small membrane-based nanovesicles naturally released from cells. Extracellular vesicles mimetics (EVMs) are artificial vesicles engineered from cells or in combination with lipid materials, and they mimic certain characteristics of EVs. As such, EVs facilitate intracellular communication by carrying and delivering biological materials, such as proteins, lipids, and nucleic acids, and they have been found to find organ tropism in preclinical studies. Because of their native structure and characteristics, they are considered promising drug carriers for future clinical use. This review outlines the origin and composition of natural EVs and EVM engineering and internalization. It then details different loading approaches, with examples of the drug delivery of therapeutic molecules. In addition, the advantages and disadvantages of loading drugs into EVs or EVMs as a drug delivery system are discussed. Finally, the advantages of EVMs over EVs and the future clinical translation of EVM-based drug delivery platforms are outlined.