Membrane Fusion Mediated Drug Loading in Exosomes

Exosome-based drug delivery gaining a significant interest from bioindustry. Compared with conventional delivery vehicles, exosomes offer minimized immunogenicity, increased circulation stability, and exceptional permeability across various biological barriers. Such distinct characteristics make exosomes as a promising next-generation delivery platform. Despite of the therapeutic potential, however, there are multiple challenges remained. Among many, drug loading in exosome is recognized as one of the major challenges. This is because current approaches not only show poor drug loading efficiency but lead to side effects such as hemolysis due to foreign components. In addition, the size of therapeutic molecules is also limited with conventional approaches. Therefore, developing a new way of loading technology in exosome is in urgent need.<br/><br/>Here we devised a novel drug loading approach utilizing a highly fusogenic lyotropic liquid crystal nanoparticles. We inspired from the fact that endosome and exosome share its biological origin. Because lipid-based lyotropic liquid crystal nanoparticles are known to easily fuse with endosome, we hypothesized that it can also easily fuse with exosome thereby delivering its cargo. Our synchrotron SAXS and FRET based study revealed that fusion-mediated drug loading shows a high loading efficiency with only innate materials. Our results indicate that the fusion-mediated loading method can be a fruitful approach for exosome therapeutics.