Efficient cell death mediated by bioengineered killer extracellular vesicles

Extracellular vesicles (EVs) are biological vehicles that are thought to mediate cell–cell communication via the transfer of biomolecules from donor to acceptor cells. Repurposing those natural vesicles into therapeutics delivery vectors is a high priority challenge for translational science. Here w...

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Bibliographic Details
Published in:Scientific reports 2023-01, Vol.13 (1), p.1086-1086, Article 1086
Main Authors: Dancourt, Julia, Piovesana, Ester, Lavieu, Gregory
Format: Article
Language:English
Subjects:
631/61
631/80
Ablation
Apoptosis
Cancer
Cell Communication
Cell Death
Cell interactions
Cells
Endoplasmic reticulum
Extracellular vesicles
Extracellular Vesicles - metabolism
Humanities and Social Sciences
Humans
Laboratories
Mortality
multidisciplinary
Neoplasms - metabolism
Plasmids
Protein biosynthesis
Protein synthesis
Proteins
Science
Science (multidisciplinary)
Toxins
Tumors
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Summary:Extracellular vesicles (EVs) are biological vehicles that are thought to mediate cell–cell communication via the transfer of biomolecules from donor to acceptor cells. Repurposing those natural vesicles into therapeutics delivery vectors is a high priority challenge for translational science. Here we engineer donor cells to produce copious amount of fusogenic EVs loaded with the catalytic domain of the Diphteria Toxin, known to trigger cell death through protein synthesis inhibition. We show that, when incubated with cancer acceptor cells, these Killer EVs block protein synthesis and lead to cell death. This proof of concept establishes the efficacy of Killer EVs in vitro, and suggests that further development may lead to tumor ablation in vivo, expanding the existing cancer therapeutics arsenal.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-28306-8