Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells
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: | http://hdl.handle.net/1822/51164 |
Resumo: | Liposomes functionalized with monoclonal antibodies or their antigen-binding fragments have attracted much attention as specific drug delivery devices for treatment of various diseases including cancer. The conjugation of antibodies to liposomes is usually achieved by covalent coupling using cross-linkers in a reaction that might adversely affect the characteristics of the final product. Here we present an alternative strategy for liposome functionalization: we created a recombinant Fab antibody fragment genetically fused on its C-terminus to the hydrophobic peptide derived from pulmonary surfactant protein D, which became inserted into the liposomal bilayer during liposomal preparation and anchored the Fab onto the liposome surface. The Fab-conjugated liposomes specifically recognized antigen-positive cells and efficiently delivered their cargo, the Alexa Fluor 647 dye, into target cells in vitro and in vivo. In conclusion, our approach offers the potential for straightforward development of nanomedicines functionalized with an antibody of choice without the need of harmful cross-linkers. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cellsactive targetingliposome functionalizationimmunoliposomeantibody engineeringrecombinant Fab antibody fragmentScience & TechnologyLiposomes functionalized with monoclonal antibodies or their antigen-binding fragments have attracted much attention as specific drug delivery devices for treatment of various diseases including cancer. The conjugation of antibodies to liposomes is usually achieved by covalent coupling using cross-linkers in a reaction that might adversely affect the characteristics of the final product. Here we present an alternative strategy for liposome functionalization: we created a recombinant Fab antibody fragment genetically fused on its C-terminus to the hydrophobic peptide derived from pulmonary surfactant protein D, which became inserted into the liposomal bilayer during liposomal preparation and anchored the Fab onto the liposome surface. The Fab-conjugated liposomes specifically recognized antigen-positive cells and efficiently delivered their cargo, the Alexa Fluor 647 dye, into target cells in vitro and in vivo. In conclusion, our approach offers the potential for straightforward development of nanomedicines functionalized with an antibody of choice without the need of harmful cross-linkers.This work has received funding from the European Union's Seventh Framework Program (FP7/2007-2013; grant agreement NMP4-LA-2009-228827 NANOFOL) and Horizon 2020 Research and Innovation Program (grant agreement No 683356 - FOLSMART), further from the Portuguese Foundation for Science and Technology under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020.info:eu-repo/semantics/publishedVersionElsevierUniversidade do MinhoOhradanova-Repic, AnnaNogueira, E.Hartl, IngridGomes, Andreia C.Preto, AnaSteinhuber, EvaMühlgrabner, VanessaRepic, MarkoKuttke, MarioZwirzitz, AlexanderProuza, MarekSuchanek, MiloslavWozniak-Knopp, GordanaHorejsi, VaclavSchabbauer, GernotCavaco-Paulo, ArturStockinger, Hannes20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/51164engOhradanova-Repic, Anna; Nogueira, E.; Hartl, Ingrid; Gomes, Andreia C.; Preto, Ana; Steinhuber, Eva; Mühlgrabner, Vanessa; Repic, Marko; Kuttke, Mario; Zwirzitz, Alexander; Prouza, Marek; Suchanek, Miloslav; Wozniak-Knopp, Gordana; Horejsi, Vaclav; Schabbauer, Gernot; Cavaco-Paulo, Artur; Stockinger, Hannes, Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells. Nanomedicine-Nanotechnology Biology and Medicine, 14(1), 123-130, 2018. doi: 10.1016/j.nano.2017.09.003154996341549-964210.1016/j.nano.2017.09.00328939491http://www.nanomedjournal.com/info: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:RCAAP2023-07-21T12:09:43Zoai:repositorium.sdum.uminho.pt:1822/51164Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:01:12.350033Repositório 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 |
Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells |
title |
Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells |
spellingShingle |
Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells Ohradanova-Repic, Anna active targeting liposome functionalization immunoliposome antibody engineering recombinant Fab antibody fragment Science & Technology |
title_short |
Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells |
title_full |
Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells |
title_fullStr |
Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells |
title_full_unstemmed |
Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells |
title_sort |
Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells |
author |
Ohradanova-Repic, Anna |
author_facet |
Ohradanova-Repic, Anna Nogueira, E. Hartl, Ingrid Gomes, Andreia C. Preto, Ana Steinhuber, Eva Mühlgrabner, Vanessa Repic, Marko Kuttke, Mario Zwirzitz, Alexander Prouza, Marek Suchanek, Miloslav Wozniak-Knopp, Gordana Horejsi, Vaclav Schabbauer, Gernot Cavaco-Paulo, Artur Stockinger, Hannes |
author_role |
author |
author2 |
Nogueira, E. Hartl, Ingrid Gomes, Andreia C. Preto, Ana Steinhuber, Eva Mühlgrabner, Vanessa Repic, Marko Kuttke, Mario Zwirzitz, Alexander Prouza, Marek Suchanek, Miloslav Wozniak-Knopp, Gordana Horejsi, Vaclav Schabbauer, Gernot Cavaco-Paulo, Artur Stockinger, Hannes |
author2_role |
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 |
Ohradanova-Repic, Anna Nogueira, E. Hartl, Ingrid Gomes, Andreia C. Preto, Ana Steinhuber, Eva Mühlgrabner, Vanessa Repic, Marko Kuttke, Mario Zwirzitz, Alexander Prouza, Marek Suchanek, Miloslav Wozniak-Knopp, Gordana Horejsi, Vaclav Schabbauer, Gernot Cavaco-Paulo, Artur Stockinger, Hannes |
dc.subject.por.fl_str_mv |
active targeting liposome functionalization immunoliposome antibody engineering recombinant Fab antibody fragment Science & Technology |
topic |
active targeting liposome functionalization immunoliposome antibody engineering recombinant Fab antibody fragment Science & Technology |
description |
Liposomes functionalized with monoclonal antibodies or their antigen-binding fragments have attracted much attention as specific drug delivery devices for treatment of various diseases including cancer. The conjugation of antibodies to liposomes is usually achieved by covalent coupling using cross-linkers in a reaction that might adversely affect the characteristics of the final product. Here we present an alternative strategy for liposome functionalization: we created a recombinant Fab antibody fragment genetically fused on its C-terminus to the hydrophobic peptide derived from pulmonary surfactant protein D, which became inserted into the liposomal bilayer during liposomal preparation and anchored the Fab onto the liposome surface. The Fab-conjugated liposomes specifically recognized antigen-positive cells and efficiently delivered their cargo, the Alexa Fluor 647 dye, into target cells in vitro and in vivo. In conclusion, our approach offers the potential for straightforward development of nanomedicines functionalized with an antibody of choice without the need of harmful cross-linkers. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018 2018-01-01T00:00:00Z |
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 |
http://hdl.handle.net/1822/51164 |
url |
http://hdl.handle.net/1822/51164 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Ohradanova-Repic, Anna; Nogueira, E.; Hartl, Ingrid; Gomes, Andreia C.; Preto, Ana; Steinhuber, Eva; Mühlgrabner, Vanessa; Repic, Marko; Kuttke, Mario; Zwirzitz, Alexander; Prouza, Marek; Suchanek, Miloslav; Wozniak-Knopp, Gordana; Horejsi, Vaclav; Schabbauer, Gernot; Cavaco-Paulo, Artur; Stockinger, Hannes, Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells. Nanomedicine-Nanotechnology Biology and Medicine, 14(1), 123-130, 2018. doi: 10.1016/j.nano.2017.09.003 15499634 1549-9642 10.1016/j.nano.2017.09.003 28939491 http://www.nanomedjournal.com/ |
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 |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132409423200256 |