Peptide anchor for folate-targeted liposomal delivery
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: | http://hdl.handle.net/1822/37622 |
Resumo: | Specific folate receptors are abundantly overexpressed in chronically activated macrophages and in most cancer cells. Directed folate receptor targeting using liposomes is usually achieved using folate linked to a phospholipid or cholesterol anchor. This link is formed using a large spacer like polyethylene glycol. Here, we report an innovative strategy for targeted liposome delivery that uses a hydrophobic fragment of surfactant protein D linked to folate. Our proposed spacer is a small 4 amino acid residue linker. The peptide conjugate inserts deeply into the lipid bilayer without affecting liposomal integrity, with high stability and specificity. To compare the drug delivery potential of both liposomal targeting systems, we encapsulated the nuclear dye Hoechst 34580. The eventual increase in blue fluorescence would only be detectable upon liposome disruption, leading to specific binding of this dye to DNA. Our delivery system was proven to be more efficient (2-fold) in Caco-2 cells than classic systems where the folate moiety is linked to liposomes by polyethylene glycol. |
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Peptide anchor for folate-targeted liposomal deliveryScience & TechnologySpecific folate receptors are abundantly overexpressed in chronically activated macrophages and in most cancer cells. Directed folate receptor targeting using liposomes is usually achieved using folate linked to a phospholipid or cholesterol anchor. This link is formed using a large spacer like polyethylene glycol. Here, we report an innovative strategy for targeted liposome delivery that uses a hydrophobic fragment of surfactant protein D linked to folate. Our proposed spacer is a small 4 amino acid residue linker. The peptide conjugate inserts deeply into the lipid bilayer without affecting liposomal integrity, with high stability and specificity. To compare the drug delivery potential of both liposomal targeting systems, we encapsulated the nuclear dye Hoechst 34580. The eventual increase in blue fluorescence would only be detectable upon liposome disruption, leading to specific binding of this dye to DNA. Our delivery system was proven to be more efficient (2-fold) in Caco-2 cells than classic systems where the folate moiety is linked to liposomes by polyethylene glycol.Eugenia Nogueira (SFRH/BD/81269/2011) and Ana Loureiro (SFRH/BD/81479/2011) 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. The authors thank the FCT Strategic Project of UID/BIO/04469/2013 unit, the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and the Project "BioHealth - Biotechnology and Bioengineering approaches to improve health quality", Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER. This work was also supported by FCT I.P. through the strategic funding UID/BIA/04050/2013. We also thank Noemy Gueriba for her technical assistance in various experiments.ACS PublicationsUniversidade do MinhoNogueira, E.Mangialavori, Irene C.Loureiro, AnaAzóia, Nuno G.Sarria, Marisa P.Nogueira, PatríciaFreitas, JaimeHarmark, JohanShimanovich, UlyanaRollett, AlexandraLacroix, GhislaineBernardes, Gonçalo J. L.Guebitz, GeorgHebert, HansMoreira, AlexandraCarmo, Alexandre M.Rossi, Juan Pablo F. C.Gomes, AndreiaPreto, AnaCavaco-Paulo, Artur2015-08-042015-08-04T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/37622engNogueira, E.; Irene C. Mangialavori; Loureiro, A.; Azoia, Nuno G.; Passos, M.; Patrícia Nogueira; Jaime Freitas; Harmark, J.; Ulyana Shimanovich; Ulyana Shimanovich; Alexandra Rollett; Ghislaine Lacroix; Bernardes, Gonçalo J. L.; Guebitz, Georg; Hebert, H.; Alexandra Moreira; Alexandre M. Carmo; Juan Pablo F. C. Rossi; Andreia Gomes; Ana Preto; Paulo, Artur Cavaco, Peptide anchor for folate-targeted liposomal delivery. Biomacromolecules, 16(9), 2904-2910, 20151526-46021525-77971526-460210.1021/acs.biomac.5b0082326241560http://pubs.acs.org/journal/bomaf6info: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:RCAAP2023-07-21T12:18:18Zoai:repositorium.sdum.uminho.pt:1822/37622Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:11:07.152506Repositório 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 |
Peptide anchor for folate-targeted liposomal delivery |
title |
Peptide anchor for folate-targeted liposomal delivery |
spellingShingle |
Peptide anchor for folate-targeted liposomal delivery Nogueira, E. Science & Technology |
title_short |
Peptide anchor for folate-targeted liposomal delivery |
title_full |
Peptide anchor for folate-targeted liposomal delivery |
title_fullStr |
Peptide anchor for folate-targeted liposomal delivery |
title_full_unstemmed |
Peptide anchor for folate-targeted liposomal delivery |
title_sort |
Peptide anchor for folate-targeted liposomal delivery |
author |
Nogueira, E. |
author_facet |
Nogueira, E. Mangialavori, Irene C. Loureiro, Ana Azóia, Nuno G. Sarria, Marisa P. Nogueira, Patrícia Freitas, Jaime Harmark, Johan Shimanovich, Ulyana Rollett, Alexandra Lacroix, Ghislaine Bernardes, Gonçalo J. L. Guebitz, Georg Hebert, Hans Moreira, Alexandra Carmo, Alexandre M. Rossi, Juan Pablo F. C. Gomes, Andreia Preto, Ana Cavaco-Paulo, Artur |
author_role |
author |
author2 |
Mangialavori, Irene C. Loureiro, Ana Azóia, Nuno G. Sarria, Marisa P. Nogueira, Patrícia Freitas, Jaime Harmark, Johan Shimanovich, Ulyana Rollett, Alexandra Lacroix, Ghislaine Bernardes, Gonçalo J. L. Guebitz, Georg Hebert, Hans Moreira, Alexandra Carmo, Alexandre M. Rossi, Juan Pablo F. C. Gomes, Andreia Preto, Ana 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, E. Mangialavori, Irene C. Loureiro, Ana Azóia, Nuno G. Sarria, Marisa P. Nogueira, Patrícia Freitas, Jaime Harmark, Johan Shimanovich, Ulyana Rollett, Alexandra Lacroix, Ghislaine Bernardes, Gonçalo J. L. Guebitz, Georg Hebert, Hans Moreira, Alexandra Carmo, Alexandre M. Rossi, Juan Pablo F. C. Gomes, Andreia Preto, Ana Cavaco-Paulo, Artur |
dc.subject.por.fl_str_mv |
Science & Technology |
topic |
Science & Technology |
description |
Specific folate receptors are abundantly overexpressed in chronically activated macrophages and in most cancer cells. Directed folate receptor targeting using liposomes is usually achieved using folate linked to a phospholipid or cholesterol anchor. This link is formed using a large spacer like polyethylene glycol. Here, we report an innovative strategy for targeted liposome delivery that uses a hydrophobic fragment of surfactant protein D linked to folate. Our proposed spacer is a small 4 amino acid residue linker. The peptide conjugate inserts deeply into the lipid bilayer without affecting liposomal integrity, with high stability and specificity. To compare the drug delivery potential of both liposomal targeting systems, we encapsulated the nuclear dye Hoechst 34580. The eventual increase in blue fluorescence would only be detectable upon liposome disruption, leading to specific binding of this dye to DNA. Our delivery system was proven to be more efficient (2-fold) in Caco-2 cells than classic systems where the folate moiety is linked to liposomes by polyethylene glycol. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-08-04 2015-08-04T00:00:00Z |
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/1822/37622 |
url |
http://hdl.handle.net/1822/37622 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Nogueira, E.; Irene C. Mangialavori; Loureiro, A.; Azoia, Nuno G.; Passos, M.; Patrícia Nogueira; Jaime Freitas; Harmark, J.; Ulyana Shimanovich; Ulyana Shimanovich; Alexandra Rollett; Ghislaine Lacroix; Bernardes, Gonçalo J. L.; Guebitz, Georg; Hebert, H.; Alexandra Moreira; Alexandre M. Carmo; Juan Pablo F. C. Rossi; Andreia Gomes; Ana Preto; Paulo, Artur Cavaco, Peptide anchor for folate-targeted liposomal delivery. Biomacromolecules, 16(9), 2904-2910, 2015 1526-4602 1525-7797 1526-4602 10.1021/acs.biomac.5b00823 26241560 http://pubs.acs.org/journal/bomaf6 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
ACS Publications |
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ACS Publications |
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