Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer

Introduction: Paclitaxel (PTX) is a cornerstone in the treatment of breast cancer, the most common type of cancer in women. However, this drug has serious limitations, including lack of tissue-specificity, poor water solubility, and the development of drug resistance. The transport of PTX in a polym...

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Autores: Cabeza Montilla, Laura, El-Hammadi, Mazen, Ortíz Quesada, Raúl, Cayero Otero, María Dolores, Jiménez López, Julia, Perazzoli, Gloria, Martín Banderas, Lucía, Baeyens Cabrera, José Manuel, Melguizo Alonso, Consolación, Prados, José
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/138602
Acceso en línea:https://hdl.handle.net/11441/138602
https://doi.org/10.34172/bi.2022.23433
Access Level:acceso abierto
Palabra clave:Paclitaxel
PLGA
Breast cancer
Cancer stem cells
Mice xenografts
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spelling Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancerCabeza Montilla, LauraEl-Hammadi, MazenOrtíz Quesada, RaúlCayero Otero, María DoloresJiménez López, JuliaPerazzoli, GloriaMartín Banderas, LucíaBaeyens Cabrera, José ManuelMelguizo Alonso, ConsolaciónPrados, JoséPaclitaxelPLGABreast cancerCancer stem cellsMice xenograftsIntroduction: Paclitaxel (PTX) is a cornerstone in the treatment of breast cancer, the most common type of cancer in women. However, this drug has serious limitations, including lack of tissue-specificity, poor water solubility, and the development of drug resistance. The transport of PTX in a polymeric nanoformulation could overcome these limitations. Methods: In this study, PLGA-PTX nanoparticles (NPs) were assayed in breast cancer cell lines, breast cancer stem cells (CSCs) and multicellular tumor spheroids (MTSs) analyzing cell cycle, cell uptake (Nile Red-NR-) and α-tubulin expression. In addition, PLGA-PTX NPs were tested in vivo using C57BL/6 mice, including a biodistribution assay. Results: PTX-PLGA NPs induced a significant decrease in the PTX IC50 of cancer cell lines (1.31 and 3.03-fold reduction in MDA-MB-231 and E0771 cells, respectively) and CSCs. In addition, MTSs treated with PTX-PLGA exhibited a more disorganized surface and significantly higher cell death rates compared to free PTX (27.9% and 16.3% less in MTSs from MCF-7 and E0771, respectively). PTX-PLGA nanoformulation preserved PTX’s mechanism of action and increased its cell internalization. Interestingly, PTX-PLGA NPs not only reduced the tumor volume of treated mice but also increased the antineoplastic drug accumulation in their lungs, liver, and spleen. In addition, mice treated with PTX-loaded NPs showed blood parameters similar to the control mice, in contrast with free PTX. Conclusion: These results suggest that our PTX-PLGA NPs could be a suitable strategy for breast cancer therapy, improving antitumor drug efficiency and reducing systemic toxicity without altering its mechanism of action.Junta de Andalucía PI-0102-2017, P18-HO-3882Instituto de Salud Carlos III PI19/01478Universidad de Ciencias Médicas de TabrizFarmacia y Tecnología FarmacéuticaUniversidad de SevillaJunta de AndalucíaInstituto de Salud Carlos III2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/138602https://doi.org/10.34172/bi.2022.23433reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésBioImpacts, 12.PI-0102-2017P18-HO-3882PI19/01478http://doi.org/10.34172/bi.2022.23433info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1386022026-06-17T12:51:07Z
dc.title.none.fl_str_mv Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer
title Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer
spellingShingle Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer
Cabeza Montilla, Laura
Paclitaxel
PLGA
Breast cancer
Cancer stem cells
Mice xenografts
title_short Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer
title_full Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer
title_fullStr Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer
title_full_unstemmed Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer
title_sort Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer
dc.creator.none.fl_str_mv Cabeza Montilla, Laura
El-Hammadi, Mazen
Ortíz Quesada, Raúl
Cayero Otero, María Dolores
Jiménez López, Julia
Perazzoli, Gloria
Martín Banderas, Lucía
Baeyens Cabrera, José Manuel
Melguizo Alonso, Consolación
Prados, José
author Cabeza Montilla, Laura
author_facet Cabeza Montilla, Laura
El-Hammadi, Mazen
Ortíz Quesada, Raúl
Cayero Otero, María Dolores
Jiménez López, Julia
Perazzoli, Gloria
Martín Banderas, Lucía
Baeyens Cabrera, José Manuel
Melguizo Alonso, Consolación
Prados, José
author_role author
author2 El-Hammadi, Mazen
Ortíz Quesada, Raúl
Cayero Otero, María Dolores
Jiménez López, Julia
Perazzoli, Gloria
Martín Banderas, Lucía
Baeyens Cabrera, José Manuel
Melguizo Alonso, Consolación
Prados, José
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Farmacia y Tecnología Farmacéutica
Universidad de Sevilla
Junta de Andalucía
Instituto de Salud Carlos III
dc.subject.none.fl_str_mv Paclitaxel
PLGA
Breast cancer
Cancer stem cells
Mice xenografts
topic Paclitaxel
PLGA
Breast cancer
Cancer stem cells
Mice xenografts
description Introduction: Paclitaxel (PTX) is a cornerstone in the treatment of breast cancer, the most common type of cancer in women. However, this drug has serious limitations, including lack of tissue-specificity, poor water solubility, and the development of drug resistance. The transport of PTX in a polymeric nanoformulation could overcome these limitations. Methods: In this study, PLGA-PTX nanoparticles (NPs) were assayed in breast cancer cell lines, breast cancer stem cells (CSCs) and multicellular tumor spheroids (MTSs) analyzing cell cycle, cell uptake (Nile Red-NR-) and α-tubulin expression. In addition, PLGA-PTX NPs were tested in vivo using C57BL/6 mice, including a biodistribution assay. Results: PTX-PLGA NPs induced a significant decrease in the PTX IC50 of cancer cell lines (1.31 and 3.03-fold reduction in MDA-MB-231 and E0771 cells, respectively) and CSCs. In addition, MTSs treated with PTX-PLGA exhibited a more disorganized surface and significantly higher cell death rates compared to free PTX (27.9% and 16.3% less in MTSs from MCF-7 and E0771, respectively). PTX-PLGA nanoformulation preserved PTX’s mechanism of action and increased its cell internalization. Interestingly, PTX-PLGA NPs not only reduced the tumor volume of treated mice but also increased the antineoplastic drug accumulation in their lungs, liver, and spleen. In addition, mice treated with PTX-loaded NPs showed blood parameters similar to the control mice, in contrast with free PTX. Conclusion: These results suggest that our PTX-PLGA NPs could be a suitable strategy for breast cancer therapy, improving antitumor drug efficiency and reducing systemic toxicity without altering its mechanism of action.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/138602
https://doi.org/10.34172/bi.2022.23433
url https://hdl.handle.net/11441/138602
https://doi.org/10.34172/bi.2022.23433
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv BioImpacts, 12.
PI-0102-2017
P18-HO-3882
PI19/01478
http://doi.org/10.34172/bi.2022.23433
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universidad de Ciencias Médicas de Tabriz
publisher.none.fl_str_mv Universidad de Ciencias Médicas de Tabriz
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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