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| 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
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.
| Ord. | Autor | Género | Institución - País |
|---|---|---|---|
| 1 | Carrasco-Rojas, Javiera | - |
Universidad del Desarrollo - Chile
|
| 2 | Zavala, Gabriela | Mujer |
Universidad del Desarrollo - Chile
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| 3 | Contreras-Lopez, Rafael | - |
Universidad del Desarrollo - Chile
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| 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
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| 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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| 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 |
| 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). |