Rage targeting therapeutic exosome for drug delivery

Abstract

Statement of Purpose: Among extracellular vesicles (EVs), membrane-derived vesicles that secreted by various types of cells for cell-cell signaling, exosome is the smallest subtype with size of 30 to 100 nm in diameter. Since exosomes were small and native to the animals, they have several advantages as drug delivery carrier. There have been several trials to decorated exosome with ligands by production of a fusion protein of a ligand and an exosome-membrane protein, Lamp2b.(1, 2) As a potential therapeutic target, RAGE is a pattern-recognition receptor that binds to endogenous damage associated molecular patterns (DAMP); signal molecules that initiate a noninfectious inflammatory response. It was previously reported that RAGE-binding peptide (RBP) derived from high-mobility group box-1 (HMGB1) suppress inflammatory response by working as an antagonist of DAMP.(3) We hypothesized that RBP-decorated exosome could deliver drug specifically to RAGE-overexpressed cells. Thus, in this research, RAGE-targeting exosome was produced by expression of a fusion protein of RBP and Lamp2b. To evaluate targeting drug delivery efficiency of RBP-decorated exosome (RBP-exo), curcumin, a natural polyphenolic drug, was loaded into exosomes and delivered to inflammatory cells.