Regulation of cargo selection in exosome biogenesis

Tiny entities called extracellular vesicles (EVs), particularly exosomes, have emerged as powerful messengers. These minuscule vesicles play pivotal roles in shuttling an impressive array of bioactive molecules between cells, influencing various physiological processes and disease states. As our understanding of exosomes deepens, their potential as disease biomarkers, therapeutic agents, and drug delivery vehicles becomes increasingly apparent.

Exosomes are like tiny parcels, brimming with a diverse assortment of cargo molecules. Within their interior, one can find a complex mix of membrane proteins, lipids, nucleic acids, cytosolic proteins, and other signaling molecules—all carefully packaged and poised to exert their effects upon reaching their target cells. Despite the profound impact that exosomes wield, the precise mechanisms governing the selective sorting and packaging of cargo within these vesicles remain a subject of intense investigation.

Researchers at the Ulsan National Institute of Science and Technology discuss exosome cargo sorting, shedding light on the molecular mechanisms that govern this process and the resulting biological functions. With a particular focus on their relevance in cancer and other diseases, they explore how exosomes contribute to disease progression and how they might be harnessed for therapeutic purposes.

Exosome engineering strategies for loading cancer therapeutic cargo into exosomes

Fig. 3

Exosomes can be engineered to target internal and modified surface cargoes for cancer therapy. Cargo loading strategies are achieved by incubating therapeutic agents (e.g., pharmacological inhibitors, miRNAs, and recombinant proteins) directly with isolated exosomes (post-loading) or by exposing them to exosome-secreting donor cells, followed by the isolation of loaded exosomes (pre-loading). Post-loading methods require physical treatments to disrupt membrane integrity and allow the cargo to enter the interior of exosomes. Alternatively, exosome-producing cells with genetic expression constructs that encode therapeutic cargoes linked to an exosome sorting domain can be generated. This leads to sorting therapeutic cargo into exosomes. Modified exosomes containing tumor antigens can stimulate antigen-presenting cells and drive antitumor immune responses in the human body. Engineered exosomes can also directly release antitumor cargo to attack cancer cells.

By unraveling the mysteries of exosome cargo sorting, the researchers aim to uncover new insights into the physiological and pathological roles of these tiny vesicles. Furthermore, understanding the mechanisms underlying exosome cargo sorting is crucial for identifying potential therapeutic targets and advancing the development of exosome-based therapeutics.

Lee YJ, Shin KJ, Chae YC. (2024) Regulation of cargo selection in exosome biogenesis and its biomedical applications in cancer. Exp Mol Med [Epub ahead of print]. [article]

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