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The cellular uptake machinery for exosome cargo delivery represents a complex suite of biological processes and molecular interactions that facilitate intercellular communication. Exosomes, a subset of extracellular vesicles, carry bioactive molecules such as proteins, lipids, and various RNA species from donor to recipient cells (Mulcahy et al., 2014). The uptake process typically involves three main stages: recruitment to the recipient cell surface via specific receptors or adhesion molecules, internalization through various endocytic pathways, and the subsequent delivery of cargo to the cytoplasm or endosomal compartments (McKiernan et al., 2023). Key molecular players in this machinery include tetraspanins like CD63 and CD81, as well as the ESCRT complex and Rab GTPases (Kalluri & LeBleu, 2020). This machinery is critically involved in physiological processes like immune signaling and tissue repair, but it is also exploited in pathological states. In oncology, exosome-mediated delivery promotes tumor microenvironment remodeling and metastasis, while in neurodegenerative diseases, it contributes to the spread of misfolded proteins (Gurung et al., 2014). Consequently, this machinery is being targeted both to inhibit disease progression and to serve as a sophisticated platform for the delivery of therapeutic agents, such as siRNA or small molecule drugs. Research into modulating this pathway often utilizes inhibitors of endocytosis like Dynasore or competitive binders like heparin to prevent vesicle internalization.
Inhibition of endocytic pathways, competitive binding to cell surface proteoglycans, and disruption of vesicle-cell membrane fusion.
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