On the mechanisms of internalization and intracellular delivery mediated by pH-sensitive liposomes
Autor(a) principal: | |
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Data de Publicação: | 2001 |
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/10316/5796 https://doi.org/10.1016/S0005-2736(01)00389-3 |
Resumo: | We investigated the molecular mechanisms by which pH-sensitive liposomes surpass the cytoplasmic and endosomal membranes to deliver their aqueous contents into the cytoplasm. Various liposome formulations were evaluated for their efficacy to mediate intracellular delivery of encapsulated material, including a novel sterically stabilized pH-sensitive formulation ((DOPE:CHEMS:DSPE-PEG2000 (6:4:0.3)) that was previously developed in our laboratories. In an attempt to fully characterize the nature of liposome-cell interactions different approaches based on a dual-labeling fluorescence assay were used. Our results indicate that the efficacy of interaction of pH-sensitive liposomes, both plain and sterically stabilized, with cells is strongly determined by the inclusion of DOPE in their composition, independently of the type of the amphiphilic stabilizer used. In fact, DOPE-containing liposomes shown to be non-pH sensitive by biophysical assays, mediated cytoplasmic delivery of their contents as efficiently as well known pH-sensitive formulations (e.g. DOPE:CHEMS). However, among the different formulations studied, DOPE:CHEMS liposomes were those exhibiting the highest extent of cell association. Moreover, our results with cells pretreated with metabolic inhibitors or lysosomotropic agents clearly indicate that DOPE-containing liposomes are internalized essentially by endocytosis and that acidification of the endosomes is not the only mechanism involved in the destabilization of the liposomes inside the cell. |
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On the mechanisms of internalization and intracellular delivery mediated by pH-sensitive liposomesIntracellular deliverypH-sensitive liposomeDioleoylphosphatidylethanolamineDifferentiated THP-1 cellFlow cytometryAmphiphilic stabilizerWe investigated the molecular mechanisms by which pH-sensitive liposomes surpass the cytoplasmic and endosomal membranes to deliver their aqueous contents into the cytoplasm. Various liposome formulations were evaluated for their efficacy to mediate intracellular delivery of encapsulated material, including a novel sterically stabilized pH-sensitive formulation ((DOPE:CHEMS:DSPE-PEG2000 (6:4:0.3)) that was previously developed in our laboratories. In an attempt to fully characterize the nature of liposome-cell interactions different approaches based on a dual-labeling fluorescence assay were used. Our results indicate that the efficacy of interaction of pH-sensitive liposomes, both plain and sterically stabilized, with cells is strongly determined by the inclusion of DOPE in their composition, independently of the type of the amphiphilic stabilizer used. In fact, DOPE-containing liposomes shown to be non-pH sensitive by biophysical assays, mediated cytoplasmic delivery of their contents as efficiently as well known pH-sensitive formulations (e.g. DOPE:CHEMS). However, among the different formulations studied, DOPE:CHEMS liposomes were those exhibiting the highest extent of cell association. Moreover, our results with cells pretreated with metabolic inhibitors or lysosomotropic agents clearly indicate that DOPE-containing liposomes are internalized essentially by endocytosis and that acidification of the endosomes is not the only mechanism involved in the destabilization of the liposomes inside the cell.http://www.sciencedirect.com/science/article/B6T1T-444F2DX-3/1/2a98bd7812d23c02787a66f8d126a7b72001info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/5796http://hdl.handle.net/10316/5796https://doi.org/10.1016/S0005-2736(01)00389-3engBiochimica et Biophysica Acta (BBA) - Biomembranes. 1515:1 (2001) 23-37Simões, SérgioSlepushkin, VladimirDüzgünes, NejatPedroso de Lima, Maria C.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:RCAAP2021-09-17T11:05:01Zoai:estudogeral.uc.pt:10316/5796Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:47:18.559652Repositório 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 |
On the mechanisms of internalization and intracellular delivery mediated by pH-sensitive liposomes |
title |
On the mechanisms of internalization and intracellular delivery mediated by pH-sensitive liposomes |
spellingShingle |
On the mechanisms of internalization and intracellular delivery mediated by pH-sensitive liposomes Simões, Sérgio Intracellular delivery pH-sensitive liposome Dioleoylphosphatidylethanolamine Differentiated THP-1 cell Flow cytometry Amphiphilic stabilizer |
title_short |
On the mechanisms of internalization and intracellular delivery mediated by pH-sensitive liposomes |
title_full |
On the mechanisms of internalization and intracellular delivery mediated by pH-sensitive liposomes |
title_fullStr |
On the mechanisms of internalization and intracellular delivery mediated by pH-sensitive liposomes |
title_full_unstemmed |
On the mechanisms of internalization and intracellular delivery mediated by pH-sensitive liposomes |
title_sort |
On the mechanisms of internalization and intracellular delivery mediated by pH-sensitive liposomes |
author |
Simões, Sérgio |
author_facet |
Simões, Sérgio Slepushkin, Vladimir Düzgünes, Nejat Pedroso de Lima, Maria C. |
author_role |
author |
author2 |
Slepushkin, Vladimir Düzgünes, Nejat Pedroso de Lima, Maria C. |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Simões, Sérgio Slepushkin, Vladimir Düzgünes, Nejat Pedroso de Lima, Maria C. |
dc.subject.por.fl_str_mv |
Intracellular delivery pH-sensitive liposome Dioleoylphosphatidylethanolamine Differentiated THP-1 cell Flow cytometry Amphiphilic stabilizer |
topic |
Intracellular delivery pH-sensitive liposome Dioleoylphosphatidylethanolamine Differentiated THP-1 cell Flow cytometry Amphiphilic stabilizer |
description |
We investigated the molecular mechanisms by which pH-sensitive liposomes surpass the cytoplasmic and endosomal membranes to deliver their aqueous contents into the cytoplasm. Various liposome formulations were evaluated for their efficacy to mediate intracellular delivery of encapsulated material, including a novel sterically stabilized pH-sensitive formulation ((DOPE:CHEMS:DSPE-PEG2000 (6:4:0.3)) that was previously developed in our laboratories. In an attempt to fully characterize the nature of liposome-cell interactions different approaches based on a dual-labeling fluorescence assay were used. Our results indicate that the efficacy of interaction of pH-sensitive liposomes, both plain and sterically stabilized, with cells is strongly determined by the inclusion of DOPE in their composition, independently of the type of the amphiphilic stabilizer used. In fact, DOPE-containing liposomes shown to be non-pH sensitive by biophysical assays, mediated cytoplasmic delivery of their contents as efficiently as well known pH-sensitive formulations (e.g. DOPE:CHEMS). However, among the different formulations studied, DOPE:CHEMS liposomes were those exhibiting the highest extent of cell association. Moreover, our results with cells pretreated with metabolic inhibitors or lysosomotropic agents clearly indicate that DOPE-containing liposomes are internalized essentially by endocytosis and that acidification of the endosomes is not the only mechanism involved in the destabilization of the liposomes inside the cell. |
publishDate |
2001 |
dc.date.none.fl_str_mv |
2001 |
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/10316/5796 http://hdl.handle.net/10316/5796 https://doi.org/10.1016/S0005-2736(01)00389-3 |
url |
http://hdl.handle.net/10316/5796 https://doi.org/10.1016/S0005-2736(01)00389-3 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Biochimica et Biophysica Acta (BBA) - Biomembranes. 1515:1 (2001) 23-37 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
aplication/PDF |
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 |
repository.mail.fl_str_mv |
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1799133750546661376 |