The formation of extracellular vesicles (EVs) and exosomes is based on continuous cell membrane renewal. EVs have three forms: microvesicles, exosomes, and tumor bodies. Microvesicles arise from the inward budding of the membrane. Exosomes are produced by the outward budding of the membrane. Tumor bodies are produced by tumor cells. The invagination of the cell membrane forms the endosome, which then assembles the components within the cell. This results in the formation of multivesicular bodies (MVBs). MVBs then fuse with the cell membrane. EVs within MVBs are released from the cell. EVs (exosomes) contain nucleic acids, lipids, and proteins from the source cell. These EVs, which carry information molecules, play an important role in the communication of information between cells. Based on the performance of exosomes as molecular carriers, therapeutic drugs (e.g., small interfering RNAs) are encapsulated in exosomes in vitro for targeted delivery to related cells. This opens a new horizon for novel precision therapy methods.
These tumor-associated miRNAs and proteins are transported by exosomes, creating an environment that favors tumor metastasis. Interestingly, certain properties of exosomes prompt novel possibilities in the treatment of cancer. Pi et al. (48) found that attaching antibody-like (i.e., Y-shaped) RNA nanoparticles to microvesicles can deliver effective RNA therapeutic agents such as small interfering RNA (siRNA) specifically to cancer cells. By using RNA nanotechnology, researchers have successfully generated extracellular vesicles capable of successfully targeting three types of cancer therapeutics in animal models. Further, its influence on the metabolism of tumor cells cannot be underestimated. Chen et al. (49) investigated the mechanism of the aerobic glycolysis of breast cancer tumor cells with a high quantity of macrophages. This study demonstrates that tumor-associated macrophages can transmit signals through EVs containing lncRNA. This signal enhances the aerobic glycolysis of breast cancer cells and improves the ability of antiapoptosis. The study also highlights the potential of lncRNAs as signal transducers, which propagate between immune cells and tumor cells by EVs and promote the aerobic glycolysis of tumor cells.
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The study of exRNA could lead to the search for new diagnostic markers or new therapeutic targets. However, before translating its use into clinical practice, the mechanisms and pathways of exRNA treatment should be understood. It is still unknown how to introduce this biomarker into clinical disease surveillance (10, 91, 92). Further, interspecies exRNA transfer may occur through contact and feeding, opening a new entry point for the transboundary transfer of exRNA. Although information exchange and transmission serve as a bridge between species, it is not fully understood whether or how they play an important role in biological interactions (90, 93, 94).
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