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Artificial cell-derived vesicles by extrusion, a novel docetaxel drug delivery system for lung cancer
Indexado
WoS WOS:001428557300001
Scopus SCOPUS_ID:85217418481
DOI 10.1016/J.JDDST.2025.106693
Año 2025
Tipo artículo de investigación

Citas Totales

Autores Afiliación Chile

Instituciones Chile

% Participación
Internacional

Autores
Afiliación Extranjera

Instituciones
Extranjeras


Abstract



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 <200 nm and stable composition, with zeta potentials between-26 and-33 mV. DTX-EXT contained 14 +/- 9.1 p.m. DTX per mu g 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.

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Disciplinas de Investigación



WOS
Pharmacology & Pharmacy
Scopus
Sin Disciplinas
SciELO
Sin Disciplinas

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Publicaciones WoS (Ediciones: ISSHP, ISTP, AHCI, SSCI, SCI), Scopus, SciELO Chile.

Colaboración Institucional



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Autores - Afiliación



Ord. Autor Género Institución - País
1 Carrasco-Rojas, Javiera - Universidad del Desarrollo - Chile
2 Zavala, Gabriela Mujer Universidad del Desarrollo - Chile
3 Contreras-Lopez, Rafael - Universidad del Desarrollo - Chile
4 Olivares, Belen - Universidad del Desarrollo - Chile
5 Aarsund, Miriam - Univ Oslo - Noruega
Universitetet i Oslo - Noruega
6 Inngjerdingen, Marit - Univ Oslo - Noruega
Universitetet i Oslo - Noruega
7 Nyman, Tuula A. - Univ Oslo - Noruega
Oslo Univ Hosp - Noruega
Universitetet i Oslo - Noruega
8 Sandoval, Felipe I. - Universidad del Desarrollo - Chile
9 Ramirez, Orlando - Universidad del Desarrollo - Chile
10 Alarcon-Moyano, Jessica - Universidad de Los Andes, Chile - Chile
11 Diaz-Calderon, Paulo - Universidad de Los Andes, Chile - Chile
12 Jara-Sandoval, Jose Antonio - Universidad de Chile - Chile
13 Schuh, Christina M. A. P. Mujer Universidad del Desarrollo - Chile

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Financiamiento



Fuente
Fondo Nacional de Desarrollo Científico y Tecnológico
Universidad del Desarrollo
Helse Sor-Ost RHF
Agencia Nacional de Investigación y Desarrollo
Convenio Beca UDD-PhD program "Science and Innovation in Medicine" at Universidad del Desarrollo
Research Council of Norway INFRASTRUKTUR-program
European Molecular Biology Organization (EMBO) Scientific Exchange Grant
Internal independent grant of Universidad Del Desarrollo
Scholarships Beca de Doctorado Nacional, ANID
Independent funding agency ANID Chile (Agencia Nacional de Investigacion y Desarrollo) under the independent grant scheme FONDECYT regular
Core Facilities program of the South-Eastern Norway Regional Health Authority

Muestra la fuente de financiamiento declarada en la publicación.

Agradecimientos



Agradecimiento
This work was financially supported by the independent funding agency ANID Chile (Agencia Nacional de Investigacion y Desarrollo) under the independent grant scheme FONDECYT regular (#1220803) . Internal independent grant of Universidad Del Desarrollo (concurso interno UDD CI2023) . European Molecular Biology Organization (EMBO) Scientific Exchange Grant 10294. Scholarships Beca de Doctorado Nacional, ANID (21200483) and Convenio Beca UDD-PhD program "Science and Innovation in Medicine" at Universidad del Desarrollo. Mass spectrometry-based proteomic analyses were performed by the Proteomics Core Facility, Department of Immunology, University of Oslo/Oslo University Hospital, which is supported by the Core Facilities program of the South-Eastern Norway Regional Health Authority. This core facility is also a member of the National Network of Advanced Proteomics Infrastructure (NAPI) , which is funded by the Research Council of Norway INFRASTRUKTUR-program (project number:295910).
This work was financially supported by the independent funding agency ANID Chile (Agencia Nacional de Investigaci\u00F3n y Desarrollo) under the independent grant scheme FONDECYT regular (#1220803). Internal independent grant of Universidad Del Desarrollo (concurso interno UDD CI2023). European Molecular Biology Organization (EMBO) Scientific Exchange Grant 10294. Scholarships Beca de Doctorado Nacional, ANID (21200483) and Convenio Beca UDD - PhD program \u201CScience and Innovation in Medicine\u201D at Universidad del Desarrollo. Mass spectrometry-based proteomic analyses were performed by the Proteomics Core Facility, Department of Immunology, University of Oslo/Oslo University Hospital, which is supported by the Core Facilities program of the South-Eastern Norway Regional Health Authority. This core facility is also a member of the National Network of Advanced Proteomics Infrastructure (NAPI), which is funded by the Research Council of Norway INFRASTRUKTUR-program (project number: 295910).

Muestra la fuente de financiamiento declarada en la publicación.