Figure 1.

Extracellular vesicle (EV) internalization pathways into recipient cells. Exogenous EVs have been shown to be internalized by cells via multiple endocytic pathways depending on cell type. These pathways include the following: 1-phagocytosis, a process used by professional phagocytic cells that involves the engulfment and digestion of extracellular material into plasma membrane-derived vacuoles called phagosomes; 2-macropinocytosis, a process during which the cell extends large membrane ruffles that fold back onto the cell surface and fuse to form pockets; 3-clathrin-mediated endocytosis, a process that requires interactions between ligands on the EV surface and specific receptors present on the plasma membrane which subsequently results in EV-packed clathrin-coated vesicles; 4-caveolae-dependent endocytosis, a process that is characterized by flask/cave-like invaginations marked by the presence of caveolin-1 and 5-lipid raft-mediated endocytosis, which takes place in a cholesterol- and sphingolipid-enriched microdomain that is regulated by various molecules. Internalization via different endocytotic pathways will target exogenous EVs in the endosomal compartment. EVs may also enter cells via fusion with the plasma membrane to deliver their contents.