Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis

© 2020 by the authors.

Detalhes bibliográficos
Autores: Manzarares, Darío, Pérez-Carrión, María Dolores, Jiménez Blanco, José L., Ortiz-Mellet, Carmen, García Fernández, José Manuel, Ceña, Valentín
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2020
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/225686
Acesso em linha:http://hdl.handle.net/10261/225686
Access Level:Acceso aberto
Palavra-chave:SiRNA
β-cyclodextrin
Endocytosis
Transfection efficiency
Micropinocytosis
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spelling Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via MacropinocytosisManzarares, DaríoPérez-Carrión, María DoloresJiménez Blanco, José L.Ortiz-Mellet, CarmenGarcía Fernández, José ManuelCeña, ValentínSiRNAβ-cyclodextrinEndocytosisTransfection efficiencyMicropinocytosis© 2020 by the authors.Small interfering ribonucleic acid (siRNA) has the potential to revolutionize therapeutics since it can knockdown very efficiently the target protein. It is starting to be widely used to interfere with cell infection by HIV. However, naked siRNAs are unable to get into the cell, requiring the use of carriers to protect them from degradation and transporting them across the cell membrane. There is no information about which is the most efficient endocytosis route for high siRNA transfection efficiency. One of the most promising carriers to efficiently deliver siRNA are cyclodextrin derivatives. We have used nanocomplexes composed of siRNA and a β-cyclodextrin derivative, AMC6, with a very high transfection efficiency to selectively knockdown clathrin heavy chain, caveolin 1, and p21 Activated Kinase 1 to specifically block clathrin-mediated, caveolin-mediated and macropinocytosis endocytic pathways. The main objective was to identify whether there is a preferential endocytic pathway associated with high siRNA transfection efficiency. We have found that macropinocytosis is the preferential entry pathway for the nanoparticle and its associated siRNA cargo. However, blockade of macropinocytosis does not affect AMC6-mediated transfection efficiency, suggesting that macropinocytosis blockade can be functionally compensated by an increase in clathrin- and caveolin-mediated endocytosis.This research was funded, in part, by contract numbers PID2019-105858RB-I00 (MCI, AEI, FEDER, UE) and RTI2018-097609-B-C21 (MICIU, AEI, FEDER, UE) to C.O.M. and J.M.G.F. and grants from the Spanish Ministerio de Economía y Competitividad (project SAF2017-89288-R from MINECO/AEI/FEDER/UE), from Junta de Comunidades de Castilla-La Mancha (project SBPLY/19/180501/000067), and ISCIII (AC19/00075) and ERANET Euronanomed Program (project NANO4GLIO) to V.C. It also benefited from the framework of COST Action Nano2Clinic (CA17140), supported by COST (European Cooperation in Science and Technology).Publisher’s versionMultidisciplinary Digital Publishing InstituteMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Ministerio de Economía y Competitividad (España)Junta de Comunidades de Castilla-La ManchaInstituto de Salud Carlos IIIEuropean Cooperation in Science and TechnologyConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020202020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/225686reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105858RB-I00PID2019-105858RB-I00/AEI/10.13039/501100011033info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-097609-B-C21RTI2018-097609-B-C21/AEI/10.13039/501100011033info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-89288-Rhttps://doi.org/10.3390/ijms21239306Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2256862026-05-22T06:33:51Z
dc.title.none.fl_str_mv Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis
title Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis
spellingShingle Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis
Manzarares, Darío
SiRNA
β-cyclodextrin
Endocytosis
Transfection efficiency
Micropinocytosis
title_short Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis
title_full Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis
title_fullStr Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis
title_full_unstemmed Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis
title_sort Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis
dc.creator.none.fl_str_mv Manzarares, Darío
Pérez-Carrión, María Dolores
Jiménez Blanco, José L.
Ortiz-Mellet, Carmen
García Fernández, José Manuel
Ceña, Valentín
author Manzarares, Darío
author_facet Manzarares, Darío
Pérez-Carrión, María Dolores
Jiménez Blanco, José L.
Ortiz-Mellet, Carmen
García Fernández, José Manuel
Ceña, Valentín
author_role author
author2 Pérez-Carrión, María Dolores
Jiménez Blanco, José L.
Ortiz-Mellet, Carmen
García Fernández, José Manuel
Ceña, Valentín
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Ministerio de Economía y Competitividad (España)
Junta de Comunidades de Castilla-La Mancha
Instituto de Salud Carlos III
European Cooperation in Science and Technology
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv SiRNA
β-cyclodextrin
Endocytosis
Transfection efficiency
Micropinocytosis
topic SiRNA
β-cyclodextrin
Endocytosis
Transfection efficiency
Micropinocytosis
description © 2020 by the authors.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/225686
url http://hdl.handle.net/10261/225686
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105858RB-I00
PID2019-105858RB-I00/AEI/10.13039/501100011033
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-097609-B-C21
RTI2018-097609-B-C21/AEI/10.13039/501100011033
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-89288-R
https://doi.org/10.3390/ijms21239306
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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