Redox-responsive micellar nanoparticles from glycosaminoglycans for CD44 targeted drug delivery
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/1822/56284 |
Resumo: | Cancer progression is associated with overexpression of various receptors at the cell surface. Among these, CD44 is known to recognize and bind specifically hyaluronan (HA) and interact with less affinity to other glycosaminoglycans (GAGs), such as chondroitin sulfate (CS). In this study, we describe a simple method to obtain micellar nanoparticles with a GAG shell (HA or CS) as potential drug delivery systems that target cancer cells overexpressing CD44. Alkanethiol was conjugated at the reducing end of the respective GAG using highly efficient oxime chemistry. The alkane moiety confers amphiphilic behavior to the obtained conjugates and triggers their self-assembly into micellar nanoparticles, while the thiol group adds redox-responsiveness to the system. The properties of the particles depend on the used GAG: HA amphiphiles form more dense, smaller assemblies that are redox sensitive. Both systems allow encapsulation of either hydrophobic or hydrophilic cargos with high efficiency. We demonstrate that the GAGs exposed on the surface of the nanoparticles are with preserved bioactivity and recognized by the cellular receptors: the particles were internalized via CD44 dependent pathways. |
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Redox-responsive micellar nanoparticles from glycosaminoglycans for CD44 targeted drug deliveryCD44chondroitin sulfateHyaluronic acidmicellar nanoparticlesself-assemblyScience & TechnologyCancer progression is associated with overexpression of various receptors at the cell surface. Among these, CD44 is known to recognize and bind specifically hyaluronan (HA) and interact with less affinity to other glycosaminoglycans (GAGs), such as chondroitin sulfate (CS). In this study, we describe a simple method to obtain micellar nanoparticles with a GAG shell (HA or CS) as potential drug delivery systems that target cancer cells overexpressing CD44. Alkanethiol was conjugated at the reducing end of the respective GAG using highly efficient oxime chemistry. The alkane moiety confers amphiphilic behavior to the obtained conjugates and triggers their self-assembly into micellar nanoparticles, while the thiol group adds redox-responsiveness to the system. The properties of the particles depend on the used GAG: HA amphiphiles form more dense, smaller assemblies that are redox sensitive. Both systems allow encapsulation of either hydrophobic or hydrophilic cargos with high efficiency. We demonstrate that the GAGs exposed on the surface of the nanoparticles are with preserved bioactivity and recognized by the cellular receptors: the particles were internalized via CD44 dependent pathways.The authors thank the Portuguese FCT (Grants no: SFRH/BD/114847/2016, IF/00032/2013 and IF/00373/2014) and EC (ComplexiTE ERC-2012-ADG 20120216-321266, H2020-TWIN CHEM2NATURE-692333, H2020-WIDESPREAD-FoReCaST-668983 and EuroNanoMed CytoNanoHeal) for providing financial support to this project.info:eu-repo/semantics/publishedVersionACSUniversidade do MinhoCarvalho, A. M.Teixeira, R.Novoa-Carballal, R.Pires, R. A.Reis, R. L.Pashkuleva, I.2018-052018-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/56284engCarvalho A. M., Teixeira R., Novoa-Carballal R., Pires R. A., Reis R. L., Pashkuleva I. Redox-responsive micellar nanoparticles from glycosaminoglycans for CD44 targeted drug delivery, Biomacromolecules, Vol. 19, Issue 7, pp. 2991 - 2999, doi:10.1021/acs.biomac.8b00561, 20181526-460210.1021/acs.biomac.8b0056129758159https://pubs.acs.org/doi/pdf/10.1021/acs.biomac.8b00561info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:00:36Zoai:repositorium.sdum.uminho.pt:1822/56284Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:50:28.087210Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Redox-responsive micellar nanoparticles from glycosaminoglycans for CD44 targeted drug delivery |
title |
Redox-responsive micellar nanoparticles from glycosaminoglycans for CD44 targeted drug delivery |
spellingShingle |
Redox-responsive micellar nanoparticles from glycosaminoglycans for CD44 targeted drug delivery Carvalho, A. M. CD44 chondroitin sulfate Hyaluronic acid micellar nanoparticles self-assembly Science & Technology |
title_short |
Redox-responsive micellar nanoparticles from glycosaminoglycans for CD44 targeted drug delivery |
title_full |
Redox-responsive micellar nanoparticles from glycosaminoglycans for CD44 targeted drug delivery |
title_fullStr |
Redox-responsive micellar nanoparticles from glycosaminoglycans for CD44 targeted drug delivery |
title_full_unstemmed |
Redox-responsive micellar nanoparticles from glycosaminoglycans for CD44 targeted drug delivery |
title_sort |
Redox-responsive micellar nanoparticles from glycosaminoglycans for CD44 targeted drug delivery |
author |
Carvalho, A. M. |
author_facet |
Carvalho, A. M. Teixeira, R. Novoa-Carballal, R. Pires, R. A. Reis, R. L. Pashkuleva, I. |
author_role |
author |
author2 |
Teixeira, R. Novoa-Carballal, R. Pires, R. A. Reis, R. L. Pashkuleva, I. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Carvalho, A. M. Teixeira, R. Novoa-Carballal, R. Pires, R. A. Reis, R. L. Pashkuleva, I. |
dc.subject.por.fl_str_mv |
CD44 chondroitin sulfate Hyaluronic acid micellar nanoparticles self-assembly Science & Technology |
topic |
CD44 chondroitin sulfate Hyaluronic acid micellar nanoparticles self-assembly Science & Technology |
description |
Cancer progression is associated with overexpression of various receptors at the cell surface. Among these, CD44 is known to recognize and bind specifically hyaluronan (HA) and interact with less affinity to other glycosaminoglycans (GAGs), such as chondroitin sulfate (CS). In this study, we describe a simple method to obtain micellar nanoparticles with a GAG shell (HA or CS) as potential drug delivery systems that target cancer cells overexpressing CD44. Alkanethiol was conjugated at the reducing end of the respective GAG using highly efficient oxime chemistry. The alkane moiety confers amphiphilic behavior to the obtained conjugates and triggers their self-assembly into micellar nanoparticles, while the thiol group adds redox-responsiveness to the system. The properties of the particles depend on the used GAG: HA amphiphiles form more dense, smaller assemblies that are redox sensitive. Both systems allow encapsulation of either hydrophobic or hydrophilic cargos with high efficiency. We demonstrate that the GAGs exposed on the surface of the nanoparticles are with preserved bioactivity and recognized by the cellular receptors: the particles were internalized via CD44 dependent pathways. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-05 2018-05-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/1822/56284 |
url |
https://hdl.handle.net/1822/56284 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Carvalho A. M., Teixeira R., Novoa-Carballal R., Pires R. A., Reis R. L., Pashkuleva I. Redox-responsive micellar nanoparticles from glycosaminoglycans for CD44 targeted drug delivery, Biomacromolecules, Vol. 19, Issue 7, pp. 2991 - 2999, doi:10.1021/acs.biomac.8b00561, 2018 1526-4602 10.1021/acs.biomac.8b00561 29758159 https://pubs.acs.org/doi/pdf/10.1021/acs.biomac.8b00561 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
ACS |
publisher.none.fl_str_mv |
ACS |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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