Extracellular vesicle uptake machinery (EV uptake)

The extracellular vesicle (EV) uptake machinery refers to the collective set of cellular processes and molecular interactions that allow recipient cells, such as immune and stromal cells, to internalize exosomes and other EVs [1]. This machinery is not a single molecule but a complex system involving surface receptors like heparan sulfate proteoglycans (HSPGs), tetraspanins (CD9, CD63, CD81), and integrins, which facilitate the docking and subsequent internalization of EVs via clathrin-mediated endocytosis, macropinocytosis, or direct membrane fusion [1, 5]. In disease states, these mechanisms are often hijacked to promote tumor progression, metastasis, and immune evasion by transferring oncogenic proteins or RNAs between cells [4]. For instance, tumor-derived exosomes can reprogram stromal fibroblasts into cancer-associated fibroblasts (CAFs) or suppress the activity of T cells and dendritic cells. Therapeutically, this 'target' is exploited by engineering exosomes to deliver specific payloads, such as STING agonists or antisense oligonucleotides, directly into the cytoplasm of target cells, offering a biocompatible alternative to synthetic nanoparticles [2]. Conversely, inhibitors of these uptake pathways are being explored to disrupt pathological intercellular communication in cancer and inflammatory conditions. Notable challenges include the rapid clearance of vesicles by the mononuclear phagocyte system and the inherent heterogeneity of EV populations, which complicates standardized therapeutic delivery [3].

Other names

Immune and stromal cell membranes via exosome and extracellular vesicle uptake mechanismsExosome uptake mechanismEV internalization pathwayVesicle-mediated transport

Therapeutic agents utilize these mechanisms for targeted delivery of cargo (e.g., nucleic acids, proteins) to specific recipient cells, or small molecules inhibit these pathways to block the transfer of pathogenic signals (e.g., in cancer metastasis).