Table 1 An overview of natural EV features that influence targeting
From: Extracellular vesicle-based therapeutics: natural versus engineered targeting and trafficking
EV Characteristic | Example | Reference |
|---|---|---|
• Protein composition | Integrin profile |  |
 The display of different integrin complexes directs EVs to either the liver and brain or lungs. | ||
Tetraspanin profile | Â | |
 EVs containing the tetraspanin Tspan8 in complex with integrin α4 were shown to be selectively taken up by cells of the pancreas. | ||
 CD63 + EVs were taken up by neurons and glial cells, while CD63- EVs bound only to the dendrites of neurons. | ||
Fibronectin | Â | |
 Fibronectin on MVEC-derived EVs mediates binding to OPCs via HPSGs. | ||
• Lipid composition | PS-coated beads targeted and tethered to phagocytic cells via T-cell immunoglobulin mucin protein 4 receptor. | |
PS-containing liposomes competitively inhibited EV uptake by murine macrophages. | ||
• Glycan composition | Glycans on the EV surface directed EVs to CCR8-expressing GBM8 cells via a triple interaction with CCL18. | |
Glycans enriched on MSC-derived EVs were involved in targeting EVs to HeLa cells via SIGLECs. | ||
• Negative harge | Negatively charged PS- and phosphatidylglycerol-containing liposomes reduced EV uptake by murine macrophages, while neutral phosphatidylcholine liposomes did not. |