In Vivo Retargeting of Poly(beta aminoester) (OM-PBAE) Nanoparticles is Influenced by Protein Corona

One of the main bottlenecks in the translation of nanomedicines from research to clinics is the difficulty in designing nanoparticles actively vectorized to the target tissue, a key parameter to ensure efficacy and safety. In this group, a library of poly(beta aminoester) polymers is developed, and...

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Autores: Fornaguera, Cristina, Guerra-Rebollo, Marta, Lázaro, Miguel Ángel, Cascante, Anna, Rubio, Núria, Blanco, Jerónimo, Borrós, Salvador
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/202221
Acceso en línea:http://hdl.handle.net/10261/202221
Access Level:acceso abierto
Palabra clave:Retinol
Liver retargeting
Protein corona
OM-PBAE nanoparticles
Nanoparticles
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spelling In Vivo Retargeting of Poly(beta aminoester) (OM-PBAE) Nanoparticles is Influenced by Protein CoronaFornaguera, CristinaGuerra-Rebollo, MartaLázaro, Miguel ÁngelCascante, AnnaRubio, NúriaBlanco, JerónimoBorrós, SalvadorRetinolLiver retargetingProtein coronaOM-PBAE nanoparticlesNanoparticlesOne of the main bottlenecks in the translation of nanomedicines from research to clinics is the difficulty in designing nanoparticles actively vectorized to the target tissue, a key parameter to ensure efficacy and safety. In this group, a library of poly(beta aminoester) polymers is developed, and it is demonstrated that adding specific combinations of terminal oligopeptides (OM-PBAE), in vitro transfection is cell selective. The current study aims to actively direct the nanoparticles to the liver by the addition of a targeting molecule. To achieve this objective, retinol, successfully attached to OM-PBAE, is selected as hepatic targeting moiety. It is demonstrated that organ biodistribution is tailored, achieving the desired liver accumulation. Regarding cell type transfection, antigen presenting cells in the liver are those showing the highest transfection. Thanks to proteomics studies, organ but not cellular biodistribution can be explained by the formation of differential protein coronas. Therefore, organ biodistribution is governed by differential protein corona formed when retinol is present, while cellular biodistribution is controlled by the end oligopeptides type. In summary, this work is a proof of concept that demonstrates the versatility of these OM-PBAE nanoparticles, in terms of the modification of the biodistribution of OM-PBAE nanoparticles adding active targeting moieties. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimFinancial support from Ministerio de Economía, Industria y Competitividad, Gobierno de España (grants RTC‐2015‐3751‐1, SAF2015‐64927‐C2‐1‐R, SAF2015‐64927‐C2‐2‐R, Torres Quevedo 2015, and RTI2018‐094734‐B‐C22) is acknowledged. C.F. is grateful to MINECO for their Postdoctoral Fellowship (grant Torres Quevedo 2015). The support of Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) from Generalitat de Catalunya through SGR 2017 1559 grant is also acknowledged. The authors acknowledge the kind support of Marco A. Fernández and Gerard Requena for the flow cytometry measures and analysis; Ramon Bartolí for the liver digestion experimental setup; and Júlia Meler, Irene Porcar, and Elena García‐Ollé for their kind support in some experiment performance.Peer reviewedWiley-BlackwellMinisterio de Economía y Competitividad (España)Fornaguera, Cristina [0000-0002-7014-3213]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202020202019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/202221reponame: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#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/RTC-2015-3751-1info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-64927-C2-1-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-64927-C2-2-Rhttps://doi.org/10.1002/adhm.201900849Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2022212026-05-22T06:33:51Z
dc.title.none.fl_str_mv In Vivo Retargeting of Poly(beta aminoester) (OM-PBAE) Nanoparticles is Influenced by Protein Corona
title In Vivo Retargeting of Poly(beta aminoester) (OM-PBAE) Nanoparticles is Influenced by Protein Corona
spellingShingle In Vivo Retargeting of Poly(beta aminoester) (OM-PBAE) Nanoparticles is Influenced by Protein Corona
Fornaguera, Cristina
Retinol
Liver retargeting
Protein corona
OM-PBAE nanoparticles
Nanoparticles
title_short In Vivo Retargeting of Poly(beta aminoester) (OM-PBAE) Nanoparticles is Influenced by Protein Corona
title_full In Vivo Retargeting of Poly(beta aminoester) (OM-PBAE) Nanoparticles is Influenced by Protein Corona
title_fullStr In Vivo Retargeting of Poly(beta aminoester) (OM-PBAE) Nanoparticles is Influenced by Protein Corona
title_full_unstemmed In Vivo Retargeting of Poly(beta aminoester) (OM-PBAE) Nanoparticles is Influenced by Protein Corona
title_sort In Vivo Retargeting of Poly(beta aminoester) (OM-PBAE) Nanoparticles is Influenced by Protein Corona
dc.creator.none.fl_str_mv Fornaguera, Cristina
Guerra-Rebollo, Marta
Lázaro, Miguel Ángel
Cascante, Anna
Rubio, Núria
Blanco, Jerónimo
Borrós, Salvador
author Fornaguera, Cristina
author_facet Fornaguera, Cristina
Guerra-Rebollo, Marta
Lázaro, Miguel Ángel
Cascante, Anna
Rubio, Núria
Blanco, Jerónimo
Borrós, Salvador
author_role author
author2 Guerra-Rebollo, Marta
Lázaro, Miguel Ángel
Cascante, Anna
Rubio, Núria
Blanco, Jerónimo
Borrós, Salvador
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Fornaguera, Cristina [0000-0002-7014-3213]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Retinol
Liver retargeting
Protein corona
OM-PBAE nanoparticles
Nanoparticles
topic Retinol
Liver retargeting
Protein corona
OM-PBAE nanoparticles
Nanoparticles
description One of the main bottlenecks in the translation of nanomedicines from research to clinics is the difficulty in designing nanoparticles actively vectorized to the target tissue, a key parameter to ensure efficacy and safety. In this group, a library of poly(beta aminoester) polymers is developed, and it is demonstrated that adding specific combinations of terminal oligopeptides (OM-PBAE), in vitro transfection is cell selective. The current study aims to actively direct the nanoparticles to the liver by the addition of a targeting molecule. To achieve this objective, retinol, successfully attached to OM-PBAE, is selected as hepatic targeting moiety. It is demonstrated that organ biodistribution is tailored, achieving the desired liver accumulation. Regarding cell type transfection, antigen presenting cells in the liver are those showing the highest transfection. Thanks to proteomics studies, organ but not cellular biodistribution can be explained by the formation of differential protein coronas. Therefore, organ biodistribution is governed by differential protein corona formed when retinol is present, while cellular biodistribution is controlled by the end oligopeptides type. In summary, this work is a proof of concept that demonstrates the versatility of these OM-PBAE nanoparticles, in terms of the modification of the biodistribution of OM-PBAE nanoparticles adding active targeting moieties. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/202221
url http://hdl.handle.net/10261/202221
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#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/RTC-2015-3751-1
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-64927-C2-1-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-64927-C2-2-R
https://doi.org/10.1002/adhm.201900849
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Wiley-Blackwell
publisher.none.fl_str_mv Wiley-Blackwell
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
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