On the mechanisms of internalization and intracellular delivery mediated by pH-sensitive liposomes

Detalhes bibliográficos
Autor(a) principal: Simões, Sérgio
Data de Publicação: 2001
Outros Autores: Slepushkin, Vladimir, Düzgünes, Nejat, Pedroso de Lima, Maria C.
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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spelling 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
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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