Citraconylated exosomes for improved internalization into macrophages

Abstract

Considering the close relation between macrophages and inflammatory diseases, the design of carriers for the delivery of drugs, genes, and small molecules into macrophages is crucial. In this study, the surface charge of exosome (EXO) was easily modified to highly negative charge by citraconylation. Prepared citraconylated EXO (cit-EXO) exhibited a significantly reduced surface charge down to − 50 from − 15 mV of EXO surface charge, despite similar hydrodynamic size. In the absence of serum proteins, both EXO and cit-EXO were similarly internalized into RAW264.7 cells and DC2.4 cells. However, cit-EXO exhibited superior intracellular uptake to that of EXO for RAW264.7 cells in the presence of serum proteins because of highly negative charges. However, there were no significant differences in intracellular uptake of EXO and cit-EXO for DC2.4 cells. Taken together, simple surface modification onto EXOs via citraconylation improved delivery of nanosized EXO (~ 50 nm) into macrophages, which could serve as a promising strategy for the development of carriers for efficient macrophage delivery.