Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cells
Autor(a) principal: | |
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Data de Publicação: | 2005 |
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/10316/5758 https://doi.org/10.1016/j.ejpb.2004.08.012 |
Resumo: | The main aim of this work was to develop novel targeted sterically stabilised pH-sensitive liposomes tailored to promote efficient intracellular delivery of therapeutic molecules into human T-leukaemia cells. Our results indicate that the targeting moiety (thiolated transferrin) was successfully coupled to the distal reactive maleimide terminus of poly(ethylene glycol)-phospholipid conjugates incorporated in the liposomal bilayer. Results from atomic force microscopy studies, performed to characterise vesicle surface topology, indicated that, to a certain extent, thiolated transferrin has the ability to associate in a non-specific manner with the lipid membrane of pegylated liposomes. This is an issue not commonly reported in the literature but which is crucial to demonstrate the targeting proof of principle. Nevertheless, fluorimetric studies together with confocal microscopy clearly demonstrate that liposomes bearing covalently coupled transferrin associate more extensively to human T-leukaemia cells in vitro than non-targeted liposomes. Cell mechanistic studies indicate that targeted liposomes bind specifically to transferrin receptors and are internalised via receptor-dependent endocytotic pathway. In addition, the biophysical features exhibited by the developed liposomes, namely their ability to promote pH-triggered cytoplasmic delivery of loaded material, make them promising delivery systems for in vivo targeting of therapeutic molecules to tumours. |
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Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cellsNanotechnologypH-sensitive liposomesTargetingTransferrinHuman T-leukaemia cellsCancer therapyThe main aim of this work was to develop novel targeted sterically stabilised pH-sensitive liposomes tailored to promote efficient intracellular delivery of therapeutic molecules into human T-leukaemia cells. Our results indicate that the targeting moiety (thiolated transferrin) was successfully coupled to the distal reactive maleimide terminus of poly(ethylene glycol)-phospholipid conjugates incorporated in the liposomal bilayer. Results from atomic force microscopy studies, performed to characterise vesicle surface topology, indicated that, to a certain extent, thiolated transferrin has the ability to associate in a non-specific manner with the lipid membrane of pegylated liposomes. This is an issue not commonly reported in the literature but which is crucial to demonstrate the targeting proof of principle. Nevertheless, fluorimetric studies together with confocal microscopy clearly demonstrate that liposomes bearing covalently coupled transferrin associate more extensively to human T-leukaemia cells in vitro than non-targeted liposomes. Cell mechanistic studies indicate that targeted liposomes bind specifically to transferrin receptors and are internalised via receptor-dependent endocytotic pathway. In addition, the biophysical features exhibited by the developed liposomes, namely their ability to promote pH-triggered cytoplasmic delivery of loaded material, make them promising delivery systems for in vivo targeting of therapeutic molecules to tumours.http://www.sciencedirect.com/science/article/B6T6C-4DVT9WH-1/1/5592c4a7248e7be29f239e55046f842c2005info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/5758http://hdl.handle.net/10316/5758https://doi.org/10.1016/j.ejpb.2004.08.012engEuropean Journal of Pharmaceutics and Biopharmaceutics. 59:2 (2005) 359-366Fonseca, CristinaMoreira, João N.Ciudad, Carlos J.Pedroso de Lima, Maria C.Simões, Sérgioinfo: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:RCAAP2021-09-17T11:05:02Zoai:estudogeral.uc.pt:10316/5758Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:47:17.507434Repositório 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 |
Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cells |
title |
Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cells |
spellingShingle |
Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cells Fonseca, Cristina Nanotechnology pH-sensitive liposomes Targeting Transferrin Human T-leukaemia cells Cancer therapy |
title_short |
Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cells |
title_full |
Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cells |
title_fullStr |
Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cells |
title_full_unstemmed |
Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cells |
title_sort |
Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cells |
author |
Fonseca, Cristina |
author_facet |
Fonseca, Cristina Moreira, João N. Ciudad, Carlos J. Pedroso de Lima, Maria C. Simões, Sérgio |
author_role |
author |
author2 |
Moreira, João N. Ciudad, Carlos J. Pedroso de Lima, Maria C. Simões, Sérgio |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Fonseca, Cristina Moreira, João N. Ciudad, Carlos J. Pedroso de Lima, Maria C. Simões, Sérgio |
dc.subject.por.fl_str_mv |
Nanotechnology pH-sensitive liposomes Targeting Transferrin Human T-leukaemia cells Cancer therapy |
topic |
Nanotechnology pH-sensitive liposomes Targeting Transferrin Human T-leukaemia cells Cancer therapy |
description |
The main aim of this work was to develop novel targeted sterically stabilised pH-sensitive liposomes tailored to promote efficient intracellular delivery of therapeutic molecules into human T-leukaemia cells. Our results indicate that the targeting moiety (thiolated transferrin) was successfully coupled to the distal reactive maleimide terminus of poly(ethylene glycol)-phospholipid conjugates incorporated in the liposomal bilayer. Results from atomic force microscopy studies, performed to characterise vesicle surface topology, indicated that, to a certain extent, thiolated transferrin has the ability to associate in a non-specific manner with the lipid membrane of pegylated liposomes. This is an issue not commonly reported in the literature but which is crucial to demonstrate the targeting proof of principle. Nevertheless, fluorimetric studies together with confocal microscopy clearly demonstrate that liposomes bearing covalently coupled transferrin associate more extensively to human T-leukaemia cells in vitro than non-targeted liposomes. Cell mechanistic studies indicate that targeted liposomes bind specifically to transferrin receptors and are internalised via receptor-dependent endocytotic pathway. In addition, the biophysical features exhibited by the developed liposomes, namely their ability to promote pH-triggered cytoplasmic delivery of loaded material, make them promising delivery systems for in vivo targeting of therapeutic molecules to tumours. |
publishDate |
2005 |
dc.date.none.fl_str_mv |
2005 |
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/10316/5758 http://hdl.handle.net/10316/5758 https://doi.org/10.1016/j.ejpb.2004.08.012 |
url |
http://hdl.handle.net/10316/5758 https://doi.org/10.1016/j.ejpb.2004.08.012 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
European Journal of Pharmaceutics and Biopharmaceutics. 59:2 (2005) 359-366 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
aplication/PDF |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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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1799133750511009792 |