Prolonged Immunomodulator Delivery Boosts Monocyte Exosome Secretion and Elevates Cathelicidin/LL-37 Content

Abstract

Human cathelicidin LL-37 offers significant benefits to the immune system and in treating various diseases, but its therapeutic potential is hindered by low activity and instability in physiological environments. Here, we introduce a strategy to boost LL-37 levels in exosomes derived from THP-1 monocytes by incubating cells with electrospun nanofibers containing immunomodulators (e.g., 1α, 25-dihydroxyvitamin D₃ and VID400). Notably, the incubation with immunomodulator-loaded nanofibers not only increased LL-37 content in exosomes but also significantly enhanced the production of engineered exosomes. Moreover, these engineered exosomes demonstrated multiple biological activities, including promoting skin cell proliferation and migration, enhancing endothelial cell tube formation, and exhibiting antibacterial properties. Collectively, this study presents an approach to increasing both the yield of engineered exosomes and their LL-37 content, potentially offering a promising therapeutic option for wound healing, tissue regeneration, and infectious disease treatment.