Exosome uptake mechanism

Exosome uptake mechanisms on recipient tissue cells refer to the diverse pathways by which cells internalize extracellular vesicles (EVs), specifically exosomes, to facilitate intercellular communication (Mulcahy et al., 2014). These mechanisms include clathrin-mediated endocytosis, caveolae-dependent endocytosis, macropinocytosis, phagocytosis, and direct plasma membrane fusion (Kalluri & LeBleu, 2020). Once internalized, exosomes release their bioactive cargo—including proteins, lipids, and various RNA species—into the recipient cell's cytoplasm, significantly altering its physiological or pathological state. In diseases like cancer, these mechanisms are exploited to promote pre-metastatic niche formation, angiogenesis, and drug resistance, while in neurodegenerative disorders, they facilitate the spread of toxic protein aggregates like tau or alpha-synuclein (Christianson et al., 2013). Targeting these uptake pathways, such as through the use of heparin to block heparan sulfate proteoglycans (HSPGs), offers a therapeutic strategy to block disease progression. However, the ubiquity of these endocytic processes in normal physiology presents significant challenges for achieving drug specificity and minimizing adverse effects (Nakase et al., 2016).

Other names

Extracellular vesicle uptakeEV internalizationExosome endocytosisEV entryExosome-cell interaction

Inhibition of endocytic pathways (clathrin- or caveolae-mediated), blockade of surface receptors such as heparan sulfate proteoglycans (HSPGs) and integrins, disruption of actin polymerization, and inhibition of membrane fusion.