Nebulized Bacterioruberin/Astaxanthin-Loaded Nanovesicles: Antitumoral Activity and Beyond

Autores
González Epelboim, Victoria Rebeca Dana; Lamas, Diego German; Huck Iriart, Cristián; Caputo, Ezequiel Nicolás; Altube, María Julia; Jerez, Horacio Emanuel; Simioni, Yamila Roxana; Ghosal, Kajal; Morilla, María José; Higa, Leticia Herminia; Romero, Eder Lilia
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The membranes of halophilic archaea are a source of novel biomaterials, mainly of isoprenoid nature, with therapeutic properties practically unraveled. Here, we explored the antitumoral activity of neutral archaeolipids (NAs, such as bacterioruberin, astaxanthin, and dihydrosqualene) present in the total archaeolipids (TAs) (a fraction from the first step of lipid extraction by the modified Blight and Dyer technique) extracted from halophilic archaea Halorubrum tebenquichense, and formulated as TA-nanoarchaeosomes (TA: polar archaeolipids (PAs): Tween 80, 5:5:4 w:w:w, TA-nanoARC). The structure of 300.3 ± 84.2 nm TA-nanoARC of 0.59 ± 0.12 polydispersity index and −20 ± 3.7 mV ζ potential as determined by SAXS modelling, revealed that NA reduced the hydrophobic core and enlarged its hydrophilic section in comparison to TA-lacking bilayers (nanoARC), while preserving the width (~50 Å) and unilamellarity. Stable to storage and nebulization, TA-nanoARC was cytotoxic on A549 cells after 48 h, with an IC50 expressed as [bacterioruberin] of 0.15 μg/mL (~0.20 µM), comparable to or lower than the IC50 of docetaxel or cisplatin. Such cytotoxicity was exerted at a concentration harmless to macrophages (mTHP-1 cells). Besides, the conditioned medium from TA-nanoARC nebulized on A549 cells reduced the expression of the CD204/SRA-1, an M2 phenotype marker, and induced pro-inflammatory activity, comparable to or to a greater extent than that induced by lipopolysaccharide, including IL-6 and TNF-α, in mTHP-1 as a model of tumor-associated macrophages. The endocytosis of TA-nanoARC by A549 cells induced Lysotracker red fluorescence to fade and blur. This suggested the internalization of the highly viscous and ordered TA-nanoARC rich in NAs and subsequent lysosomal dysfunction (and not its antioxidant activity), as responsible for the selective damage on A549 cells. These are the first results showing that nebulized TA-nanoARC, lethal to A549 cells and modulating mTHP-1 cell phenotype, may act as antitumorals in the absence of cytotoxic drugs.
Fil: González Epelboim, Victoria Rebeca Dana. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina
Fil: Lamas, Diego German. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Tecnologías Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologías Emergentes y Ciencias Aplicadas; Argentina
Fil: Huck Iriart, Cristián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Tecnologías Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologías Emergentes y Ciencias Aplicadas; Argentina
Fil: Caputo, Ezequiel Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; Argentina
Fil: Altube, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; Argentina
Fil: Jerez, Horacio Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina
Fil: Simioni, Yamila Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; Argentina
Fil: Ghosal, Kajal. Jadavpur University; India
Fil: Morilla, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina
Fil: Higa, Leticia Herminia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; Argentina
Fil: Romero, Eder Lilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; Argentina
Materia
LUNGS
INHALATION
XANTOPHYLLS
INHALATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/282492
Acceder
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spelling Nebulized Bacterioruberin/Astaxanthin-Loaded Nanovesicles: Antitumoral Activity and BeyondGonzález Epelboim, Victoria Rebeca DanaLamas, Diego GermanHuck Iriart, CristiánCaputo, Ezequiel NicolásAltube, María JuliaJerez, Horacio EmanuelSimioni, Yamila RoxanaGhosal, KajalMorilla, María JoséHiga, Leticia HerminiaRomero, Eder LiliaLUNGSINHALATIONXANTOPHYLLSINHALATIONhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3The membranes of halophilic archaea are a source of novel biomaterials, mainly of isoprenoid nature, with therapeutic properties practically unraveled. Here, we explored the antitumoral activity of neutral archaeolipids (NAs, such as bacterioruberin, astaxanthin, and dihydrosqualene) present in the total archaeolipids (TAs) (a fraction from the first step of lipid extraction by the modified Blight and Dyer technique) extracted from halophilic archaea Halorubrum tebenquichense, and formulated as TA-nanoarchaeosomes (TA: polar archaeolipids (PAs): Tween 80, 5:5:4 w:w:w, TA-nanoARC). The structure of 300.3 ± 84.2 nm TA-nanoARC of 0.59 ± 0.12 polydispersity index and −20 ± 3.7 mV ζ potential as determined by SAXS modelling, revealed that NA reduced the hydrophobic core and enlarged its hydrophilic section in comparison to TA-lacking bilayers (nanoARC), while preserving the width (~50 Å) and unilamellarity. Stable to storage and nebulization, TA-nanoARC was cytotoxic on A549 cells after 48 h, with an IC50 expressed as [bacterioruberin] of 0.15 μg/mL (~0.20 µM), comparable to or lower than the IC50 of docetaxel or cisplatin. Such cytotoxicity was exerted at a concentration harmless to macrophages (mTHP-1 cells). Besides, the conditioned medium from TA-nanoARC nebulized on A549 cells reduced the expression of the CD204/SRA-1, an M2 phenotype marker, and induced pro-inflammatory activity, comparable to or to a greater extent than that induced by lipopolysaccharide, including IL-6 and TNF-α, in mTHP-1 as a model of tumor-associated macrophages. The endocytosis of TA-nanoARC by A549 cells induced Lysotracker red fluorescence to fade and blur. This suggested the internalization of the highly viscous and ordered TA-nanoARC rich in NAs and subsequent lysosomal dysfunction (and not its antioxidant activity), as responsible for the selective damage on A549 cells. These are the first results showing that nebulized TA-nanoARC, lethal to A549 cells and modulating mTHP-1 cell phenotype, may act as antitumorals in the absence of cytotoxic drugs.Fil: González Epelboim, Victoria Rebeca Dana. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; ArgentinaFil: Lamas, Diego German. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Tecnologías Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologías Emergentes y Ciencias Aplicadas; ArgentinaFil: Huck Iriart, Cristián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Tecnologías Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologías Emergentes y Ciencias Aplicadas; ArgentinaFil: Caputo, Ezequiel Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; ArgentinaFil: Altube, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; ArgentinaFil: Jerez, Horacio Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; ArgentinaFil: Simioni, Yamila Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; ArgentinaFil: Ghosal, Kajal. Jadavpur University; IndiaFil: Morilla, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; ArgentinaFil: Higa, Leticia Herminia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; ArgentinaFil: Romero, Eder Lilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; ArgentinaMultidisciplinary Digital Publishing Institute2025-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/282492González Epelboim, Victoria Rebeca Dana; Lamas, Diego German; Huck Iriart, Cristián; Caputo, Ezequiel Nicolás; Altube, María Julia; et al.; Nebulized Bacterioruberin/Astaxanthin-Loaded Nanovesicles: Antitumoral Activity and Beyond; Multidisciplinary Digital Publishing Institute; International Journal of Molecular Sciences; 26; 17; 9-2025; 1-261422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/26/17/8607info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms26178607info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-03-31T15:22:35Zoai:ri.conicet.gov.ar:11336/282492instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-03-31 15:22:36.125CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Nebulized Bacterioruberin/Astaxanthin-Loaded Nanovesicles: Antitumoral Activity and Beyond
title Nebulized Bacterioruberin/Astaxanthin-Loaded Nanovesicles: Antitumoral Activity and Beyond
spellingShingle Nebulized Bacterioruberin/Astaxanthin-Loaded Nanovesicles: Antitumoral Activity and Beyond
González Epelboim, Victoria Rebeca Dana
LUNGS
INHALATION
XANTOPHYLLS
INHALATION
title_short Nebulized Bacterioruberin/Astaxanthin-Loaded Nanovesicles: Antitumoral Activity and Beyond
title_full Nebulized Bacterioruberin/Astaxanthin-Loaded Nanovesicles: Antitumoral Activity and Beyond
title_fullStr Nebulized Bacterioruberin/Astaxanthin-Loaded Nanovesicles: Antitumoral Activity and Beyond
title_full_unstemmed Nebulized Bacterioruberin/Astaxanthin-Loaded Nanovesicles: Antitumoral Activity and Beyond
title_sort Nebulized Bacterioruberin/Astaxanthin-Loaded Nanovesicles: Antitumoral Activity and Beyond
dc.creator.none.fl_str_mv González Epelboim, Victoria Rebeca Dana
Lamas, Diego German
Huck Iriart, Cristián
Caputo, Ezequiel Nicolás
Altube, María Julia
Jerez, Horacio Emanuel
Simioni, Yamila Roxana
Ghosal, Kajal
Morilla, María José
Higa, Leticia Herminia
Romero, Eder Lilia
author González Epelboim, Victoria Rebeca Dana
author_facet González Epelboim, Victoria Rebeca Dana
Lamas, Diego German
Huck Iriart, Cristián
Caputo, Ezequiel Nicolás
Altube, María Julia
Jerez, Horacio Emanuel
Simioni, Yamila Roxana
Ghosal, Kajal
Morilla, María José
Higa, Leticia Herminia
Romero, Eder Lilia
author_role author
author2 Lamas, Diego German
Huck Iriart, Cristián
Caputo, Ezequiel Nicolás
Altube, María Julia
Jerez, Horacio Emanuel
Simioni, Yamila Roxana
Ghosal, Kajal
Morilla, María José
Higa, Leticia Herminia
Romero, Eder Lilia
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv LUNGS
INHALATION
XANTOPHYLLS
INHALATION
topic LUNGS
INHALATION
XANTOPHYLLS
INHALATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The membranes of halophilic archaea are a source of novel biomaterials, mainly of isoprenoid nature, with therapeutic properties practically unraveled. Here, we explored the antitumoral activity of neutral archaeolipids (NAs, such as bacterioruberin, astaxanthin, and dihydrosqualene) present in the total archaeolipids (TAs) (a fraction from the first step of lipid extraction by the modified Blight and Dyer technique) extracted from halophilic archaea Halorubrum tebenquichense, and formulated as TA-nanoarchaeosomes (TA: polar archaeolipids (PAs): Tween 80, 5:5:4 w:w:w, TA-nanoARC). The structure of 300.3 ± 84.2 nm TA-nanoARC of 0.59 ± 0.12 polydispersity index and −20 ± 3.7 mV ζ potential as determined by SAXS modelling, revealed that NA reduced the hydrophobic core and enlarged its hydrophilic section in comparison to TA-lacking bilayers (nanoARC), while preserving the width (~50 Å) and unilamellarity. Stable to storage and nebulization, TA-nanoARC was cytotoxic on A549 cells after 48 h, with an IC50 expressed as [bacterioruberin] of 0.15 μg/mL (~0.20 µM), comparable to or lower than the IC50 of docetaxel or cisplatin. Such cytotoxicity was exerted at a concentration harmless to macrophages (mTHP-1 cells). Besides, the conditioned medium from TA-nanoARC nebulized on A549 cells reduced the expression of the CD204/SRA-1, an M2 phenotype marker, and induced pro-inflammatory activity, comparable to or to a greater extent than that induced by lipopolysaccharide, including IL-6 and TNF-α, in mTHP-1 as a model of tumor-associated macrophages. The endocytosis of TA-nanoARC by A549 cells induced Lysotracker red fluorescence to fade and blur. This suggested the internalization of the highly viscous and ordered TA-nanoARC rich in NAs and subsequent lysosomal dysfunction (and not its antioxidant activity), as responsible for the selective damage on A549 cells. These are the first results showing that nebulized TA-nanoARC, lethal to A549 cells and modulating mTHP-1 cell phenotype, may act as antitumorals in the absence of cytotoxic drugs.
Fil: González Epelboim, Victoria Rebeca Dana. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina
Fil: Lamas, Diego German. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Tecnologías Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologías Emergentes y Ciencias Aplicadas; Argentina
Fil: Huck Iriart, Cristián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Tecnologías Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologías Emergentes y Ciencias Aplicadas; Argentina
Fil: Caputo, Ezequiel Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; Argentina
Fil: Altube, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; Argentina
Fil: Jerez, Horacio Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina
Fil: Simioni, Yamila Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; Argentina
Fil: Ghosal, Kajal. Jadavpur University; India
Fil: Morilla, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina
Fil: Higa, Leticia Herminia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; Argentina
Fil: Romero, Eder Lilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; Argentina
description The membranes of halophilic archaea are a source of novel biomaterials, mainly of isoprenoid nature, with therapeutic properties practically unraveled. Here, we explored the antitumoral activity of neutral archaeolipids (NAs, such as bacterioruberin, astaxanthin, and dihydrosqualene) present in the total archaeolipids (TAs) (a fraction from the first step of lipid extraction by the modified Blight and Dyer technique) extracted from halophilic archaea Halorubrum tebenquichense, and formulated as TA-nanoarchaeosomes (TA: polar archaeolipids (PAs): Tween 80, 5:5:4 w:w:w, TA-nanoARC). The structure of 300.3 ± 84.2 nm TA-nanoARC of 0.59 ± 0.12 polydispersity index and −20 ± 3.7 mV ζ potential as determined by SAXS modelling, revealed that NA reduced the hydrophobic core and enlarged its hydrophilic section in comparison to TA-lacking bilayers (nanoARC), while preserving the width (~50 Å) and unilamellarity. Stable to storage and nebulization, TA-nanoARC was cytotoxic on A549 cells after 48 h, with an IC50 expressed as [bacterioruberin] of 0.15 μg/mL (~0.20 µM), comparable to or lower than the IC50 of docetaxel or cisplatin. Such cytotoxicity was exerted at a concentration harmless to macrophages (mTHP-1 cells). Besides, the conditioned medium from TA-nanoARC nebulized on A549 cells reduced the expression of the CD204/SRA-1, an M2 phenotype marker, and induced pro-inflammatory activity, comparable to or to a greater extent than that induced by lipopolysaccharide, including IL-6 and TNF-α, in mTHP-1 as a model of tumor-associated macrophages. The endocytosis of TA-nanoARC by A549 cells induced Lysotracker red fluorescence to fade and blur. This suggested the internalization of the highly viscous and ordered TA-nanoARC rich in NAs and subsequent lysosomal dysfunction (and not its antioxidant activity), as responsible for the selective damage on A549 cells. These are the first results showing that nebulized TA-nanoARC, lethal to A549 cells and modulating mTHP-1 cell phenotype, may act as antitumorals in the absence of cytotoxic drugs.
publishDate 2025
dc.date.none.fl_str_mv 2025-09
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status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/282492
González Epelboim, Victoria Rebeca Dana; Lamas, Diego German; Huck Iriart, Cristián; Caputo, Ezequiel Nicolás; Altube, María Julia; et al.; Nebulized Bacterioruberin/Astaxanthin-Loaded Nanovesicles: Antitumoral Activity and Beyond; Multidisciplinary Digital Publishing Institute; International Journal of Molecular Sciences; 26; 17; 9-2025; 1-26
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/282492
identifier_str_mv González Epelboim, Victoria Rebeca Dana; Lamas, Diego German; Huck Iriart, Cristián; Caputo, Ezequiel Nicolás; Altube, María Julia; et al.; Nebulized Bacterioruberin/Astaxanthin-Loaded Nanovesicles: Antitumoral Activity and Beyond; Multidisciplinary Digital Publishing Institute; International Journal of Molecular Sciences; 26; 17; 9-2025; 1-26
1422-0067
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms26178607
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
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dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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