Fig. 11.

Main strategies for EVs modification. Left: Strategies for modifying donor cells. Co-incubation, transfection and hypoxia are biochemical factors, which are used to load cargoes into donor cells. Mechanical stress and 3D-culture are mechanical factors that increase yield and change contents. Right: Strategies for directly modifying EVs. Direct mixing and electroporation are used to introduce cargoes into EVs. Fusion with membrane proteins and reverse surface charge are used to modify EVs membrane to improve targeting, distribution, retention, and bioavailability. Nanomaterials including liposomes can be mixed with EV membranes to generate hybrid EVs.