Abstract:
Exosomes are naturally occurring extracellular vesicles with diameters varying from 30nm to
150nm that are enclosed by a lipid bilayer membrane like that of a human cell membrane. They are secreted by different types of cell lines and cells such as neural, hematopoietic, fibroblast, epithelial, muscle, stem cell, and tumor cells, and have been found in surrounding
biological fluids. These nanoscale exosomes efficiently transport a variety of cargo, including
lipids, metabolites, functional proteins, and nucleic acids, to the target cell, where they play a
crucial role in intra- and intercellular communication. Their natural delivery capability makes
them an ideal candidate for therapeutics delivery systems compared to synthetic counterparts, which often exhibit limitations such as immunogenicity, cytotoxicity, biocompatibility, and
adverse side effects. Both natural exosomes and those that have been modified with other
substances to increase their target delivery ability have been used. This study has focused on natural delivery vehicles such as exosome-based targeted drug
delivery vehicles that provide unique opportunities for the delivery of therapeutics across
specific physical barriers and address challenges posed by synthetic drug delivery systems. In this study, exosomes were modified for targeted therapeutics delivery by surface
engineering with the peptide of Herpes simplex virus Glycoprotein D that binds to the herpes
virus entry mediator (HVEM) receptor. The cell-targeting function of these engineered
exosomes was introduced by expressing HSV glycoprotein D in HEK293T cell and followed
by isolation of exosome from supernatant of engineered cells. Characterization using
vi
scanning electron microscopy confirmed the cup-shaped morphology and size of the
exosomes, and the presence of the target gene was validated through western blotting. These
engineered exosomes exhibit selective binding to white blood cells via the HVEM receptor
that is present in blood cell populations such as white blood cells (Natural killer cells, monocytes, T cells, B cells), epithelial cells, and endothelial cells, offering potential
application in treating leukemia (, B-cell leukemia, T-cell leukemia, Myeloid leukemia), autoimmune diseases, immunodeficiency diseases, and tumor, etc. by loading therapeutic
agents into them
