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Figure 3. Escape mechanisms of extracellular vesicles. There are four proposed mechanisms for delivering EV cargo into the cytoplasm. The first mechanism involves the direct fusion of the EV with the cellular membrane, resulting in the complete release of the EV’s contents. The second mechanism, known as back fusion, occurs when the EV fuses with the endosomal membrane after being taken up via endocytosis. In the third mechanism, following endosomal uptake, EVs can induce pore formation, allowing the cargo to be transported into the cytoplasm. Finally, EVs can promote endosomal escape by buffering acidification and increasing the number of protons transported into the endosome, leading to membrane leakage through osmotic pressure caused by high ionic strength. This figure was created using Biorender. EV: Extracellular vesicle.