Artificial cell-derived vesicles by extrusion, a novel docetaxel drug delivery system for lung cancer

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dc.coverageDOI: 10.1016/j.jddst.2025.106693
dc.creatorCarrasco-Rojas, Javiera
dc.creatorZavala, Gabriela
dc.creatorContreras-Lopez, Rafael
dc.creatorOlivares, Belén
dc.creatorAarsund, Miriam
dc.creatorInngjerdingen, Marit
dc.creatorNyman, Tuula A.
dc.creatorSandoval, Felipe I.
dc.creatorRamírez, Orlando
dc.creatorAlarcón-Moyano, Jessica
dc.creatorDíaz-Calderón, Paulo
dc.creatorJara-Sandoval, José Antonio
dc.creatorSchuh, Christina M.A.P.
dc.date2025
dc.date.accessioned2025-11-18T19:44:10Z
dc.date.available2025-11-18T19:44:10Z
dc.description<p>Lung cancer (LC) has the highest mortality rate worldwide and novel therapies are being sought. Among those are cell-product-based therapies such as extracellular vesicles (EVs). Recently, it has been discovered that artificial cell-derived vesicle by extrusion (EXT) could be a potential tool to lower barriers to clinical translation. In this study we propose a formulation of human natural killer (NK) EXT encapsulating docetaxel (DTX) for LC therapy. EXT-DTXs were generated from NK cells by cell extrusion. EXTs and DTX-EXTs, were characterized and compared to EVs secreted by NK cells. All vesicles displayed a cup-shaped morphology with a mean size of &lt;200 nm and stable composition, with zeta potentials between −26 and −33 mV. DTX-EXT contained 14 ± 9.1 p.m. DTX per μg of EXT protein. The proteome of EVs, EXT and DTX-EXT was analyzed and revealed a distinct protein enrichment pattern for each group. Uptake inhibition studies identified clathrin-mediated endocytosis as the primary internalization pathway for all vesicle types in A549 and H1975 LC cells. Cytotoxicity assays demonstrated that DTX-EXTs induced significantly higher apoptosis and reduced cell viability compared to EVs and EXTs, with higher efficacy in A549 cells. Notably, DTX-EXTs induced cytotoxic effects at picomolar docetaxel concentrations, 300–600 times lower than free DTX. This study provides the first comprehensive characterization of docetaxel-loaded NK artificially cell-derived vesicle by extrusion, highlighting their potential as a novel therapeutic delivery system with enhanced anti-tumor efficacy. Future studies are warranted to further explore the therapeutic potential and safety profile of DTX-EXTs in cancer treatment.</p>eng
dc.identifierhttps://investigadores.uandes.cl/en/publications/af3da48f-582d-49cb-ba8d-7fa1dce9ca66
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/53265
dc.languageeng
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.sourcevol.106 (2025)
dc.subjectArtificially cell-derived vesicles (ACDV)
dc.subjectCell extrusion
dc.subjectClathrin-dependent endocytosis
dc.subjectDrug encapsulation
dc.subjectSDG 3 - Good Health and Well-being
dc.titleArtificial cell-derived vesicles by extrusion, a novel docetaxel drug delivery system for lung cancereng
dc.typeArticleeng
dc.typeArtículospa
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