The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in astrocytes - electrophysiological quantification
Autor(a) principal: | |
---|---|
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: | https://hdl.handle.net/1822/51339 |
Resumo: | Nanoparticle-based drug delivery systems may impose risks to patients due to potential toxicity associated with lack of clearance from cells or prolonged carrier-cell retention. This work evaluates vesicular cell uptake, retention and the possible transfer of endocytosed methylprednisolone-loaded carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles (NPs) into secretory vesicles of rat cultured astrocytes. Cells were incubated with NPs and unitary vesicle fusions/fissions with the plasma membrane were monitored employing high resolution membrane capacitance measurements. In NPs-treated cells the frequency of unitary exocytotic events was significantly increased. The presence of NPs also induce an increase in the size of exocytotic vesicles interacting with the plasma membrane, which exhibit transient fusion with prolonged fusion pore dwell-time. Live-cell confocal imaging revealed that once NPs internalize into endocytotic compartments they remain in the cell for 7 days, although a significant proportion of these merge with secretory vesicles destined for exocytosis. Co-localization studies show the route of clearance of NPs from cells via the exocytotic pathway. These findings bring new insight into the understanding of the intracellular trafficking and biological interactions of drug-loaded dendrimer NPs targeting astrocytes. |
id |
RCAP_ce34fc17202b74a31feaf7ee4e1e9b04 |
---|---|
oai_identifier_str |
oai:repositorium.sdum.uminho.pt:1822/51339 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in astrocytes - electrophysiological quantificationDendrimer nanoparticlesExocytosis/endocytosisAstrocytesHigh-resolution membrane capacitanceLive confocal imagingScience & TechnologyNanoparticle-based drug delivery systems may impose risks to patients due to potential toxicity associated with lack of clearance from cells or prolonged carrier-cell retention. This work evaluates vesicular cell uptake, retention and the possible transfer of endocytosed methylprednisolone-loaded carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles (NPs) into secretory vesicles of rat cultured astrocytes. Cells were incubated with NPs and unitary vesicle fusions/fissions with the plasma membrane were monitored employing high resolution membrane capacitance measurements. In NPs-treated cells the frequency of unitary exocytotic events was significantly increased. The presence of NPs also induce an increase in the size of exocytotic vesicles interacting with the plasma membrane, which exhibit transient fusion with prolonged fusion pore dwell-time. Live-cell confocal imaging revealed that once NPs internalize into endocytotic compartments they remain in the cell for 7 days, although a significant proportion of these merge with secretory vesicles destined for exocytosis. Co-localization studies show the route of clearance of NPs from cells via the exocytotic pathway. These findings bring new insight into the understanding of the intracellular trafficking and biological interactions of drug-loaded dendrimer NPs targeting astrocytes.The study was supported by the Slovenian Research Agency (grants P3 310, J3 6790, J3 7605) and the European Science Foundation COST STSM grant attributed to S.R. Cerqueira. The authors would also like to acknowledge the funds from the Portuguese Foundation for Science and Technology (fellowships to S.R.C. SFRH/BD/48406/2008) and the European Union's Seventh Framework Programme (FP7/2007-2013, grant agreement no. REGPOT-CT2012-316331-POLARIS). J.M.O. also thanks the FCT for the funds provided under the program Investigador FCT (IF/00423/2012 and IF/01285/2015).info:eu-repo/semantics/publishedVersionRoyal Society of ChemistryUniversidade do MinhoChowdury, Helena H.Cerqueira, Susana Isabel RibeiroSousa, NunoOliveira, J. M.Reis, R. L.Zorec, Robert2018-012018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/51339engChowdury H. H., Cerqueira S. R., Sousa N., Oliveira J. M., Reis R. L., Zorec R. The Uptake, Retention and Clearance of Drug-Loaded Dendrimer Nanoparticles in Astrocytes - Electrophysiological Quantification, Biomaterials Science, Vol. 6, Issue 2, pp. 388-397, doi:10.1039/C7BM00886D, 20182047-48302047-484910.1039/C7BM00886D29336451http://dx.doi.org/10.1039/C7BM00886Dinfo: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:RCAAP2023-07-21T11:56:04Zoai:repositorium.sdum.uminho.pt:1822/51339Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:45:40.411325Repositório 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 |
The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in astrocytes - electrophysiological quantification |
title |
The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in astrocytes - electrophysiological quantification |
spellingShingle |
The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in astrocytes - electrophysiological quantification Chowdury, Helena H. Dendrimer nanoparticles Exocytosis/endocytosis Astrocytes High-resolution membrane capacitance Live confocal imaging Science & Technology |
title_short |
The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in astrocytes - electrophysiological quantification |
title_full |
The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in astrocytes - electrophysiological quantification |
title_fullStr |
The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in astrocytes - electrophysiological quantification |
title_full_unstemmed |
The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in astrocytes - electrophysiological quantification |
title_sort |
The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in astrocytes - electrophysiological quantification |
author |
Chowdury, Helena H. |
author_facet |
Chowdury, Helena H. Cerqueira, Susana Isabel Ribeiro Sousa, Nuno Oliveira, J. M. Reis, R. L. Zorec, Robert |
author_role |
author |
author2 |
Cerqueira, Susana Isabel Ribeiro Sousa, Nuno Oliveira, J. M. Reis, R. L. Zorec, Robert |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Chowdury, Helena H. Cerqueira, Susana Isabel Ribeiro Sousa, Nuno Oliveira, J. M. Reis, R. L. Zorec, Robert |
dc.subject.por.fl_str_mv |
Dendrimer nanoparticles Exocytosis/endocytosis Astrocytes High-resolution membrane capacitance Live confocal imaging Science & Technology |
topic |
Dendrimer nanoparticles Exocytosis/endocytosis Astrocytes High-resolution membrane capacitance Live confocal imaging Science & Technology |
description |
Nanoparticle-based drug delivery systems may impose risks to patients due to potential toxicity associated with lack of clearance from cells or prolonged carrier-cell retention. This work evaluates vesicular cell uptake, retention and the possible transfer of endocytosed methylprednisolone-loaded carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles (NPs) into secretory vesicles of rat cultured astrocytes. Cells were incubated with NPs and unitary vesicle fusions/fissions with the plasma membrane were monitored employing high resolution membrane capacitance measurements. In NPs-treated cells the frequency of unitary exocytotic events was significantly increased. The presence of NPs also induce an increase in the size of exocytotic vesicles interacting with the plasma membrane, which exhibit transient fusion with prolonged fusion pore dwell-time. Live-cell confocal imaging revealed that once NPs internalize into endocytotic compartments they remain in the cell for 7 days, although a significant proportion of these merge with secretory vesicles destined for exocytosis. Co-localization studies show the route of clearance of NPs from cells via the exocytotic pathway. These findings bring new insight into the understanding of the intracellular trafficking and biological interactions of drug-loaded dendrimer NPs targeting astrocytes. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-01 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 |
https://hdl.handle.net/1822/51339 |
url |
https://hdl.handle.net/1822/51339 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Chowdury H. H., Cerqueira S. R., Sousa N., Oliveira J. M., Reis R. L., Zorec R. The Uptake, Retention and Clearance of Drug-Loaded Dendrimer Nanoparticles in Astrocytes - Electrophysiological Quantification, Biomaterials Science, Vol. 6, Issue 2, pp. 388-397, doi:10.1039/C7BM00886D, 2018 2047-4830 2047-4849 10.1039/C7BM00886D 29336451 http://dx.doi.org/10.1039/C7BM00886D |
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 |
Royal Society of Chemistry |
publisher.none.fl_str_mv |
Royal Society of Chemistry |
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 |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
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 |
|
_version_ |
1799132210666668032 |