Exosomal cellular uptake

Exosomal cellular uptake is the biological process by which cells internalize extracellular vesicles (EVs) to facilitate the horizontal transfer of bioactive cargo, including proteins, lipids, and various RNA species (Mulcahy et al., 2014). This internalization occurs through a variety of mechanisms such as clathrin-mediated endocytosis, caveolae-dependent endocytosis, macropinocytosis, and phagocytosis (Costa Verdera et al., 2017). The term "non-specific uptake" typically refers to these generalized endocytic pathways or interactions with ubiquitous surface molecules like heparan sulfate proteoglycans, rather than high-affinity, cell-specific receptor-ligand pairings (Christianson et al., 2013). In oncology, the uptake of tumor-derived exosomes by distant cells is a critical step in the formation of the pre-metastatic niche and the spread of pro-angiogenic signals (Kalluri and LeBleu, 2020). For the pharmaceutical industry, the non-specific nature of exosomal uptake remains a primary challenge in the development of EV-based therapeutics, as it often results in rapid clearance by the mononuclear phagocyte system and off-target delivery to the liver and spleen. Consequently, current research focuses on engineering exosomal surfaces with targeting moieties to override these non-specific pathways and improve therapeutic index.

Other names

Non-specific exosome internalizationExtracellular vesicle uptakeEV endocytosisExosome internalizationVesicular cargo uptake

Inhibition of generalized endocytic pathways (e.g., macropinocytosis, clathrin-mediated endocytosis) or competitive inhibition of surface-binding sites such as heparan sulfate proteoglycans to prevent vesicle internalization (Christianson et al., 2013).