Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering

Modular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize...

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Autores: Voltà-Durán, Eric|||0000-0003-0017-8274, Cano-Garrido, Olivia|||0000-0002-5504-2131, Serna, Naroa|||0000-0001-5682-8198, López-Laguna, Hèctor|||0000-0001-5249-8304, Sánchez-García, Laura|||0000-0002-8420-1701, Pesarrodona Roches, Mireia|||0000-0001-9669-8471, Sánchez Chardi, Alejandro|||0000-0002-8789-1883, Mangues, Ramon|||0000-0003-2661-9525, Villaverde, Antonio|||0000-0002-2615-4521, Vázquez, Esther|||0000-0003-1052-0424, Unzueta Elorza, Ugutz|||0000-0001-5119-2266
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:233718
Acceso en línea:https://ddd.uab.cat/record/233718
https://dx.doi.org/urn:doi:10.1007/s40843-019-9582-9
Access Level:acceso abierto
Palabra clave:Nanoparticles
Protein materials
Recombinant proteins
Drug delivery
Self-assembling
Cancer cell targeting
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spelling Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineeringVoltà-Durán, Eric|||0000-0003-0017-8274Cano-Garrido, Olivia|||0000-0002-5504-2131Serna, Naroa|||0000-0001-5682-8198López-Laguna, Hèctor|||0000-0001-5249-8304Sánchez-García, Laura|||0000-0002-8420-1701Pesarrodona Roches, Mireia|||0000-0001-9669-8471Sánchez Chardi, Alejandro|||0000-0002-8789-1883Mangues, Ramon|||0000-0003-2661-9525Villaverde, Antonio|||0000-0002-2615-4521Vázquez, Esther|||0000-0003-1052-0424Unzueta Elorza, Ugutz|||0000-0001-5119-2266NanoparticlesProtein materialsRecombinant proteinsDrug deliverySelf-assemblingCancer cell targetingModular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize as supramolecular entities and to generate multifunctional protein materials. To explore this concept, we have repositioned functional segments in the modular protein T22-GFP-H6 and characterized the resulting alternative fusions. In T22-GFP-H6, the combination of T22 and H6 promotes self-assembling as regular nanoparticles and selective binding and internalization of this material in CXCR4-overexpressing tumor cells, making them appealing as vehicles for selective drug delivery. The results show that the pleiotropic activities are dramatically affected in module-swapped constructs, proving the need of a carboxy terminal positioning of H6 for protein self-assembling, and the accommodation of T22 at the amino terminus as a requisite for CXCR4 cell binding and internalization. Furthermore, the failure of self-assembling as regular oligomers reduces cellular penetrability of the fusions while keeping the specificity of the T22-CXCR4 interaction. All these data instruct how multifunctional nanoscale protein carriers can be designed for smart, protein-driven drug delivery, not only for the treatment of CXCR4 human neoplasias, but also for the development of anti-HIV drugs and other pathologies in which CXCR4 is a relevant homing marker. 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/233718https://dx.doi.org/urn:doi:10.1007/s40843-019-9582-9reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 BIO2016-76063-RMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI15/00272Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PIE15//00028Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00650Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-865Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-229Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2018/FI_B2_05051Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2019/FI_B_35252open accesshttp://purl.org/coar/access_right/c_abf2Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.https://rightsstatements.org/vocab/InC/1.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2337182026-06-06T12:50:31Z
dc.title.none.fl_str_mv Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering
title Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering
spellingShingle Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering
Voltà-Durán, Eric|||0000-0003-0017-8274
Nanoparticles
Protein materials
Recombinant proteins
Drug delivery
Self-assembling
Cancer cell targeting
title_short Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering
title_full Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering
title_fullStr Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering
title_full_unstemmed Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering
title_sort Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering
dc.creator.none.fl_str_mv Voltà-Durán, Eric|||0000-0003-0017-8274
Cano-Garrido, Olivia|||0000-0002-5504-2131
Serna, Naroa|||0000-0001-5682-8198
López-Laguna, Hèctor|||0000-0001-5249-8304
Sánchez-García, Laura|||0000-0002-8420-1701
Pesarrodona Roches, Mireia|||0000-0001-9669-8471
Sánchez Chardi, Alejandro|||0000-0002-8789-1883
Mangues, Ramon|||0000-0003-2661-9525
Villaverde, Antonio|||0000-0002-2615-4521
Vázquez, Esther|||0000-0003-1052-0424
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
author Voltà-Durán, Eric|||0000-0003-0017-8274
author_facet Voltà-Durán, Eric|||0000-0003-0017-8274
Cano-Garrido, Olivia|||0000-0002-5504-2131
Serna, Naroa|||0000-0001-5682-8198
López-Laguna, Hèctor|||0000-0001-5249-8304
Sánchez-García, Laura|||0000-0002-8420-1701
Pesarrodona Roches, Mireia|||0000-0001-9669-8471
Sánchez Chardi, Alejandro|||0000-0002-8789-1883
Mangues, Ramon|||0000-0003-2661-9525
Villaverde, Antonio|||0000-0002-2615-4521
Vázquez, Esther|||0000-0003-1052-0424
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
author_role author
author2 Cano-Garrido, Olivia|||0000-0002-5504-2131
Serna, Naroa|||0000-0001-5682-8198
López-Laguna, Hèctor|||0000-0001-5249-8304
Sánchez-García, Laura|||0000-0002-8420-1701
Pesarrodona Roches, Mireia|||0000-0001-9669-8471
Sánchez Chardi, Alejandro|||0000-0002-8789-1883
Mangues, Ramon|||0000-0003-2661-9525
Villaverde, Antonio|||0000-0002-2615-4521
Vázquez, Esther|||0000-0003-1052-0424
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Nanoparticles
Protein materials
Recombinant proteins
Drug delivery
Self-assembling
Cancer cell targeting
topic Nanoparticles
Protein materials
Recombinant proteins
Drug delivery
Self-assembling
Cancer cell targeting
description Modular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize as supramolecular entities and to generate multifunctional protein materials. To explore this concept, we have repositioned functional segments in the modular protein T22-GFP-H6 and characterized the resulting alternative fusions. In T22-GFP-H6, the combination of T22 and H6 promotes self-assembling as regular nanoparticles and selective binding and internalization of this material in CXCR4-overexpressing tumor cells, making them appealing as vehicles for selective drug delivery. The results show that the pleiotropic activities are dramatically affected in module-swapped constructs, proving the need of a carboxy terminal positioning of H6 for protein self-assembling, and the accommodation of T22 at the amino terminus as a requisite for CXCR4 cell binding and internalization. Furthermore, the failure of self-assembling as regular oligomers reduces cellular penetrability of the fusions while keeping the specificity of the T22-CXCR4 interaction. All these data instruct how multifunctional nanoscale protein carriers can be designed for smart, protein-driven drug delivery, not only for the treatment of CXCR4 human neoplasias, but also for the development of anti-HIV drugs and other pathologies in which CXCR4 is a relevant homing marker.
publishDate 2020
dc.date.none.fl_str_mv 2
2020-01-01
2020
2020-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/233718
https://dx.doi.org/urn:doi:10.1007/s40843-019-9582-9
url https://ddd.uab.cat/record/233718
https://dx.doi.org/urn:doi:10.1007/s40843-019-9582-9
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 BIO2016-76063-R
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI15/00272
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PIE15//00028
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00650
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-865
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-229
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2018/FI_B2_05051
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2019/FI_B_35252
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://rightsstatements.org/vocab/InC/1.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://rightsstatements.org/vocab/InC/1.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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