Fig. 1

The biogenesis, internalisation, and contents of the sEVs. According to the endosomal model, sEVs originate from the invagination of the plasma membrane. After formation and maturation of double-membrane endosomal vesicles, various cargoes are sorted into intraluminal vesicles (ILVs) during the formation of multivesicular bodies (MVBs), which then fuse with the plasma membrane and released out sEVs. sEVs can also be directly budded from the plasma membrane or stored in intracellular plasma membrane–connected compartments (IPMCs) for delayed release. sEVs can transport their cargos to recipient cells, which are then internalised by direct fusion with the plasma membrane, clathrin/caveolin/lipid/receptor-dependent endocytosis, phagocytosis, or macropinocytes. The components carried by sEVs can be divided into two categories, including membrane proteins and lipids, as well as cytosolic proteins and nucleic acids. Tetraspanins, adhesion molecules, and specific receptors on the surface are involved in various cellular responses and can be used as engineered scaffolds. The cytosolic nucleic acids contain DNAs, including gDNA (genome DNA), mtDNA (mitochondrial DNA) and RNAs, including mRNA, miRNA (microRNA), lncRNA (long non-coding RNA), circRNA (circularRNA). A large number of lipids are anchored to the membrane, including cholesterol, phospholipids, phosphatidylethanolamine, polyglycerol, and diglycerides. These lipids not only function to maintain the bilayer membrane structure but also participate in various biological and immune responses