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Exosome uptake and intracellular cargo targets refers to the biological mechanisms and molecular components involved in the internalization of exosomes—small extracellular vesicles (EVs)—by recipient cells and the subsequent release of their functional cargo (Johnson et al., 2023). This process is a fundamental mode of intercellular communication, allowing for the transfer of proteins, lipids, and nucleic acids (such as miRNA and mRNA) between cells (Lima et al., 2024). Uptake is mediated by a variety of surface molecules, including heparan sulfate proteoglycans (HSPGs), integrins, tetraspanins (e.g., CD63, CD81), and lectins, which facilitate docking and trigger endocytic pathways like macropinocytosis, clathrin-mediated endocytosis, or membrane fusion (Faruque et al., 2024). Once inside the cell, the exosomal cargo must escape the endosomal system to reach its intracellular targets, such as the RNA-induced silencing complex (RISC) for miRNAs or ribosomes for mRNAs (Johnson et al., 2023). In diseases like cancer, this pathway is exploited to promote tumor progression and pre-metastatic niche formation, making it a target for therapeutic intervention (Tian et al., 2014). Conversely, the engineering of these uptake mechanisms is central to the development of exosomes as sophisticated drug delivery systems for the targeted transport of therapeutic agents (System Biosciences, 2023).
Inhibition of endocytic pathways (e.g., macropinocytosis, clathrin-mediated endocytosis), blocking of surface receptors (e.g., integrins, HSPGs), and disruption of membrane fusion or endosomal escape to prevent exosome internalization and subsequent cargo release.
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