Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice
Autor(a) principal: | |
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Data de Publicação: | 2015 |
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/1822/37777 |
Resumo: | Methotrexate is the first line of treatment of rheumatoid arthritis. Since many patients become unresponsive to methotrexate treatment, only very expensive biological therapies are effective and increased methotrexate tolerance strategies need to be identified. Here we propose the encapsulation of methotrexate in a new liposomal formulation using a hydrophobic fragment of surfactant protein conjugated to a linker and folate to enhance their tolerance and efficacy. In this study we aim to evaluate the efficiency of this system to treat rheumatoid arthritis, by targeting folate receptor present at the surface of activated macrophages, key effector cells in this pathology. The specificity of our liposomal formulation to target folate receptor was investigated both in vitro as in vivo using a mouse model of arthritis (collagen-induced arthritis in DBA/1J mice strain). In both systems, the liposomal constructs were shown to be highly specific and efficient in targeting folate receptor . These liposomal formulations also significantly increase the clinical benefit of the encapsulated methotrexate in vivo in arthritic mice, together with reduced expression of CD39 and CD73 ectonucleotidases by joint-infiltrating macrophages. Thus, our formulation might be a promising cost effective way to treat rheumatoid arthritis and delay or reduce methotrexate intolerance. |
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Enhancing methotrexate tolerance with folate tagged liposomes in arthritic miceRheumatoid ArthritisMethotrexateMacrophagesFolate ReceptorLiposomesScience & TechnologyMethotrexate is the first line of treatment of rheumatoid arthritis. Since many patients become unresponsive to methotrexate treatment, only very expensive biological therapies are effective and increased methotrexate tolerance strategies need to be identified. Here we propose the encapsulation of methotrexate in a new liposomal formulation using a hydrophobic fragment of surfactant protein conjugated to a linker and folate to enhance their tolerance and efficacy. In this study we aim to evaluate the efficiency of this system to treat rheumatoid arthritis, by targeting folate receptor present at the surface of activated macrophages, key effector cells in this pathology. The specificity of our liposomal formulation to target folate receptor was investigated both in vitro as in vivo using a mouse model of arthritis (collagen-induced arthritis in DBA/1J mice strain). In both systems, the liposomal constructs were shown to be highly specific and efficient in targeting folate receptor . These liposomal formulations also significantly increase the clinical benefit of the encapsulated methotrexate in vivo in arthritic mice, together with reduced expression of CD39 and CD73 ectonucleotidases by joint-infiltrating macrophages. Thus, our formulation might be a promising cost effective way to treat rheumatoid arthritis and delay or reduce methotrexate intolerance.Eugenia Nogueira (SFRH/BD/81269/2011), Ana Loureiro (SFRH/BD/81479/2011) and Catarina Almeida (SFRH/BPD/48533/2008) hold scholarships from Fundacao para a Ciencia e a Tecnologia (FCT). Goncalo J. L. Bernardes is a Royal Society University Research Fellow at the Department of Chemistry, University of Cambridge and an Investigador FCT at the Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa. This study was funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement NMP4-LA-2009-228827 NANOFOL. This study was also supported by FEDER through POFC-COMPETE, by national funds from FCT through the project PEst-C/BIA/UI4050/2014 and the strategic funding of ID/BIO/04469/2013 unit. We thank the Immuno-haemotherapy Department of Hospital de Sao Joao (Porto, Portugal) for providing buffy coats from healthy volunteers. We also thank Noemy Gueriba for her technical assistance in various experiments.American Scientific PublishersUniversidade do MinhoNogueira, Eugénia Sofia CostaLager, FranckLe Roux, DelphineNogueira, PatríciaFreitas, JaimeCharvet, CelineRenault, GillesLoureiro, AnaAlmeida, Catarina R.Ohradanova-Repic, AnnaMachacek, ChristianBernardes, Gonçalo J. L.Moreira, AlexandraStockinger, HannesBurnet, MichaelCarmo, Alexandre M.Gomes, Andreia CPreto, AnaBismuth, GeorgesCavaco-Paulo, Artur2015-03-182015-03-18T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/37777engNogueira, E.; Lager, Franck; Le Roux, Delphine; Nogueira, Patrícia; Freitas, Jaime; Charvet, Celine; Renault, Gilles; Loureiro, A.; Almeida, Catarina R.; Ohradanova-Repic, Anna; Machacek, Christian; Bernardes, Gonçalo J. L.; Moreira, Alexandra; Stockinger, Hannes; Burnet, Michael; Carmo, Alexandre M.; Gomes, A. C.; Preto, A.; Bismuth, Georges; Paulo, Artur Cavaco, Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice. Journal of Biomedical Nanotechnology, 11(12), 2243-2252, 20151550-70331550-704110.1166/jbn.2015.217026510317http://www.aspbs.com/jbn.htmlinfo: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:RCAAP2023-10-07T01:21:53Zoai:repositorium.sdum.uminho.pt:1822/37777Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:30:16.797608Repositório 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 |
Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice |
title |
Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice |
spellingShingle |
Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice Nogueira, Eugénia Sofia Costa Rheumatoid Arthritis Methotrexate Macrophages Folate Receptor Liposomes Science & Technology |
title_short |
Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice |
title_full |
Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice |
title_fullStr |
Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice |
title_full_unstemmed |
Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice |
title_sort |
Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice |
author |
Nogueira, Eugénia Sofia Costa |
author_facet |
Nogueira, Eugénia Sofia Costa Lager, Franck Le Roux, Delphine Nogueira, Patrícia Freitas, Jaime Charvet, Celine Renault, Gilles Loureiro, Ana Almeida, Catarina R. Ohradanova-Repic, Anna Machacek, Christian Bernardes, Gonçalo J. L. Moreira, Alexandra Stockinger, Hannes Burnet, Michael Carmo, Alexandre M. Gomes, Andreia C Preto, Ana Bismuth, Georges Cavaco-Paulo, Artur |
author_role |
author |
author2 |
Lager, Franck Le Roux, Delphine Nogueira, Patrícia Freitas, Jaime Charvet, Celine Renault, Gilles Loureiro, Ana Almeida, Catarina R. Ohradanova-Repic, Anna Machacek, Christian Bernardes, Gonçalo J. L. Moreira, Alexandra Stockinger, Hannes Burnet, Michael Carmo, Alexandre M. Gomes, Andreia C Preto, Ana Bismuth, Georges Cavaco-Paulo, Artur |
author2_role |
author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Nogueira, Eugénia Sofia Costa Lager, Franck Le Roux, Delphine Nogueira, Patrícia Freitas, Jaime Charvet, Celine Renault, Gilles Loureiro, Ana Almeida, Catarina R. Ohradanova-Repic, Anna Machacek, Christian Bernardes, Gonçalo J. L. Moreira, Alexandra Stockinger, Hannes Burnet, Michael Carmo, Alexandre M. Gomes, Andreia C Preto, Ana Bismuth, Georges Cavaco-Paulo, Artur |
dc.subject.por.fl_str_mv |
Rheumatoid Arthritis Methotrexate Macrophages Folate Receptor Liposomes Science & Technology |
topic |
Rheumatoid Arthritis Methotrexate Macrophages Folate Receptor Liposomes Science & Technology |
description |
Methotrexate is the first line of treatment of rheumatoid arthritis. Since many patients become unresponsive to methotrexate treatment, only very expensive biological therapies are effective and increased methotrexate tolerance strategies need to be identified. Here we propose the encapsulation of methotrexate in a new liposomal formulation using a hydrophobic fragment of surfactant protein conjugated to a linker and folate to enhance their tolerance and efficacy. In this study we aim to evaluate the efficiency of this system to treat rheumatoid arthritis, by targeting folate receptor present at the surface of activated macrophages, key effector cells in this pathology. The specificity of our liposomal formulation to target folate receptor was investigated both in vitro as in vivo using a mouse model of arthritis (collagen-induced arthritis in DBA/1J mice strain). In both systems, the liposomal constructs were shown to be highly specific and efficient in targeting folate receptor . These liposomal formulations also significantly increase the clinical benefit of the encapsulated methotrexate in vivo in arthritic mice, together with reduced expression of CD39 and CD73 ectonucleotidases by joint-infiltrating macrophages. Thus, our formulation might be a promising cost effective way to treat rheumatoid arthritis and delay or reduce methotrexate intolerance. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-03-18 2015-03-18T00:00:00Z |
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/1822/37777 |
url |
https://hdl.handle.net/1822/37777 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Nogueira, E.; Lager, Franck; Le Roux, Delphine; Nogueira, Patrícia; Freitas, Jaime; Charvet, Celine; Renault, Gilles; Loureiro, A.; Almeida, Catarina R.; Ohradanova-Repic, Anna; Machacek, Christian; Bernardes, Gonçalo J. L.; Moreira, Alexandra; Stockinger, Hannes; Burnet, Michael; Carmo, Alexandre M.; Gomes, A. C.; Preto, A.; Bismuth, Georges; Paulo, Artur Cavaco, Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice. Journal of Biomedical Nanotechnology, 11(12), 2243-2252, 2015 1550-7033 1550-7041 10.1166/jbn.2015.2170 26510317 http://www.aspbs.com/jbn.html |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
American Scientific Publishers |
publisher.none.fl_str_mv |
American Scientific Publishers |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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