Macrophage-derived fusogenic nanovesicle for detection of atherosclerotic plaque progression

Abstract

Macrophages have an inherent ability to fuse together and form multinucleated giant cells under certain stimuli. During this process, macrophages become fusogenic and upregulate specific fusion-mediating surface proteins that facilitate homotypic fusion. Cell-derived vesicles can be produced with cell membranes at specific time points of cell physiology, resulting in vesicles that reflect the physiological state of the cell. Here, we propose a novel macrophage-targeted drug delivery system using fusogenic macrophage-derived nanovesicles (F-MNVs). F-MNVs retain fusion mediators in the fusogenic state, allowing them to serve as naturally occurring macrophage targeting moieties. These F-MNVs exhibit selective uptake by macrophages among mixed cell populations. In addition, unlike conventional nanoparticle uptake, F-MNVs fuse with macrophage membranes and deliver their cargo directly into the cytosol, bypassing endosomal entrapment and lysosomal degradation. In a rabbit model of atherosclerosis, injected F-MNVs efficiently targeted macrophage-rich plaques, confirming their potential as a precise, biologically derived platform for drug delivery in inflammatory diseases.