Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment

Glioblastoma (GB) is a malignant brain tumor with low survival rates and a high recurrence ratio due to limited therapeutic arsenal. The repurposed drug disulfiram (DSF), approved for alcoholism treatment, shows promising anticancer and antimicrobial activity, but its poor biopharmaceutical profile...

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Autores: González Prada, Iago, Barcelos Ribeiro, Arthur, Dion, Marine, Magariños Ferro, Beatriz, Lapoujade, Clémentine, Rousseau, Audrey, Concheiro Nine, Ángel Joaquín, Garcion, Emmanuel, Álvarez Lorenzo, Carmen
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:dnet:minerva_____::e3b176fbfed8a55974fa9c5f6aa74814
Acceso en línea:https://hdl.handle.net/10347/46977
Access Level:acceso abierto
Palabra clave:Copper
Cyclodextrin
Disulfiram
Electrospinning
Glioblastoma
Silk fibroin
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spelling Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatmentGonzález Prada, IagoBarcelos Ribeiro, ArthurDion, MarineMagariños Ferro, BeatrizLapoujade, ClémentineRousseau, AudreyConcheiro Nine, Ángel JoaquínGarcion, EmmanuelÁlvarez Lorenzo, CarmenCopperCyclodextrinDisulfiramElectrospinningGlioblastomaSilk fibroinGlioblastoma (GB) is a malignant brain tumor with low survival rates and a high recurrence ratio due to limited therapeutic arsenal. The repurposed drug disulfiram (DSF), approved for alcoholism treatment, shows promising anticancer and antimicrobial activity, but its poor biopharmaceutical profile hinders its clinical use. This work aimed to develop DSF-loaded silk fibroin (SF) electrospun fibers for controlled release in the postsurgical resection cavity. Incorporating hydroxypropyl-β-cyclodextrin (HPβCD), which formed inclusion complexes with DSF, enhanced drug release rate and antimicrobial activity (>3 logCFUs reduction) against Staphylococcus aureus and Pseudomonas aeruginosa. Addition of CuCl2 enabled in situ formation of Cu(DDC)2 complexes, further boosting antimicrobial and in vitro antitumoral effects of the nanofibers (≤ 500 nm) while maintaining adequate mechanical properties. Selective toxicity of DSF and DSF-loaded fibers against glioblastoma cells, while sparing against astrocytes, highlights the potential of the nanofibers for targeted brain cancer therapy. Increased potency of DSF at low concentrations when combined with SF fibers, HPβCD and copper was remarkable. Thus, DSF delivery and bioavailability can be significantly optimized through electrospun nanofibers, which may also allow for more precise dosing. Combination with radiotherapy was also explored to assess the translational potential of DSF as part of a combination therapy regimen for glioblastoma. In vivo studies in a rat model simulating GB surgery confirmed the safety of selected formulations in healthy brain tissue. However, findings suggest that DSF-loaded fibers alone may be insufficient for complete tumor eradication, indicating the need for combination with existing therapies to target residual tumor cells effectively.ElsevierUniversidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía FarmacéuticaUniversidade de Santiago de Compostela. Departamento de Microbioloxía e ParasitoloxíaUniversidade de Santiago de Compostela. Instituto de Materiais (iMATUS)20252025-03-1220252025-03-12journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10347/46977reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostelainstname:Universidad de Santiago de Compostela (USC)InglésengAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 PID2020-113881RB-I00 ARQUITECTURAS 5D PARA MEDICINA REGENERATIVA Y TERAPIA LOCALIZADAopen accesshttp://purl.org/coar/access_right/c_abf2© 2025 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC licensehttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:dnet:minerva_____::e3b176fbfed8a55974fa9c5f6aa748142026-06-15T12:47:27Z
dc.title.none.fl_str_mv Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment
title Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment
spellingShingle Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment
González Prada, Iago
Copper
Cyclodextrin
Disulfiram
Electrospinning
Glioblastoma
Silk fibroin
title_short Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment
title_full Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment
title_fullStr Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment
title_full_unstemmed Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment
title_sort Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment
dc.creator.none.fl_str_mv González Prada, Iago
Barcelos Ribeiro, Arthur
Dion, Marine
Magariños Ferro, Beatriz
Lapoujade, Clémentine
Rousseau, Audrey
Concheiro Nine, Ángel Joaquín
Garcion, Emmanuel
Álvarez Lorenzo, Carmen
author González Prada, Iago
author_facet González Prada, Iago
Barcelos Ribeiro, Arthur
Dion, Marine
Magariños Ferro, Beatriz
Lapoujade, Clémentine
Rousseau, Audrey
Concheiro Nine, Ángel Joaquín
Garcion, Emmanuel
Álvarez Lorenzo, Carmen
author_role author
author2 Barcelos Ribeiro, Arthur
Dion, Marine
Magariños Ferro, Beatriz
Lapoujade, Clémentine
Rousseau, Audrey
Concheiro Nine, Ángel Joaquín
Garcion, Emmanuel
Álvarez Lorenzo, Carmen
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica
Universidade de Santiago de Compostela. Departamento de Microbioloxía e Parasitoloxía
Universidade de Santiago de Compostela. Instituto de Materiais (iMATUS)
dc.subject.none.fl_str_mv Copper
Cyclodextrin
Disulfiram
Electrospinning
Glioblastoma
Silk fibroin
topic Copper
Cyclodextrin
Disulfiram
Electrospinning
Glioblastoma
Silk fibroin
description Glioblastoma (GB) is a malignant brain tumor with low survival rates and a high recurrence ratio due to limited therapeutic arsenal. The repurposed drug disulfiram (DSF), approved for alcoholism treatment, shows promising anticancer and antimicrobial activity, but its poor biopharmaceutical profile hinders its clinical use. This work aimed to develop DSF-loaded silk fibroin (SF) electrospun fibers for controlled release in the postsurgical resection cavity. Incorporating hydroxypropyl-β-cyclodextrin (HPβCD), which formed inclusion complexes with DSF, enhanced drug release rate and antimicrobial activity (>3 logCFUs reduction) against Staphylococcus aureus and Pseudomonas aeruginosa. Addition of CuCl2 enabled in situ formation of Cu(DDC)2 complexes, further boosting antimicrobial and in vitro antitumoral effects of the nanofibers (≤ 500 nm) while maintaining adequate mechanical properties. Selective toxicity of DSF and DSF-loaded fibers against glioblastoma cells, while sparing against astrocytes, highlights the potential of the nanofibers for targeted brain cancer therapy. Increased potency of DSF at low concentrations when combined with SF fibers, HPβCD and copper was remarkable. Thus, DSF delivery and bioavailability can be significantly optimized through electrospun nanofibers, which may also allow for more precise dosing. Combination with radiotherapy was also explored to assess the translational potential of DSF as part of a combination therapy regimen for glioblastoma. In vivo studies in a rat model simulating GB surgery confirmed the safety of selected formulations in healthy brain tissue. However, findings suggest that DSF-loaded fibers alone may be insufficient for complete tumor eradication, indicating the need for combination with existing therapies to target residual tumor cells effectively.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-03-12
2025
2025-03-12
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10347/46977
url https://hdl.handle.net/10347/46977
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 PID2020-113881RB-I00 ARQUITECTURAS 5D PARA MEDICINA REGENERATIVA Y TERAPIA LOCALIZADA
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
http://creativecommons.org/licenses/by-nc/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname:Universidad de Santiago de Compostela (USC)
instname_str Universidad de Santiago de Compostela (USC)
reponame_str Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
collection Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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