Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer

By the appropriate selection of functional peptides and proper accommodation sites, we have generated a set of multifunctional proteins that combine selectivity for CXCR4 cell binding and relevant endosomal escape capabilities linked to the viral peptide HA2. In particular, the construct T22-GFP-HA2...

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Autores: Sala, Rita, Sánchez-García, Laura|||0000-0002-8420-1701, Serna, Naroa|||0000-0001-5682-8198, Céspedes, María Virtudes|||0000-0003-2956-5833, Casanova Rigat, Isolda|||0000-0002-1196-4724, Roldán, Mònica, Sánchez Chardi, Alejandro|||0000-0002-8789-1883, Unzueta Elorza, Ugutz|||0000-0001-5119-2266, Vázquez, Esther|||0000-0003-1052-0424, Mangues, Ramon|||0000-0003-2661-9525, Villaverde, Antonio|||0000-0002-2615-4521
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:233714
Acceso en línea:https://ddd.uab.cat/record/233714
https://dx.doi.org/urn:doi:10.1016/j.actbio.2019.09.002
Access Level:acceso abierto
Palabra clave:Protein materials
Self-assembling
Fusogenic peptide
Colorectal cancer
CXCR4
Active targeting
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spelling Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancerSala, RitaSánchez-García, Laura|||0000-0002-8420-1701Serna, Naroa|||0000-0001-5682-8198Céspedes, María Virtudes|||0000-0003-2956-5833Casanova Rigat, Isolda|||0000-0002-1196-4724Roldán, MònicaSánchez Chardi, Alejandro|||0000-0002-8789-1883Unzueta Elorza, Ugutz|||0000-0001-5119-2266Vázquez, Esther|||0000-0003-1052-0424Mangues, Ramon|||0000-0003-2661-9525Villaverde, Antonio|||0000-0002-2615-4521Protein materialsSelf-assemblingFusogenic peptideColorectal cancerCXCR4Active targetingBy the appropriate selection of functional peptides and proper accommodation sites, we have generated a set of multifunctional proteins that combine selectivity for CXCR4 cell binding and relevant endosomal escape capabilities linked to the viral peptide HA2. In particular, the construct T22-GFP-HA2-H6 forms nanoparticles that upon administration in mouse models of human, CXCR4 colorectal cancer, accumulates in primary tumor at levels significantly higher than the parental T22-GFP-H6 HA2-lacking version. The in vivo application of a CXCR4 antagonist has confirmed the prevalence of the CXCR4 tumor tissue selectivity over unspecific cell penetration, upon systemic administration of the material. Such specificity is combined with improved endosomal escape, what overall results in a precise and highly efficient tumor biodistribution. These data strongly support the functional recruitment as a convenient approach to generate protein materials for clinical applications. More precisely, they also support the unexpected concept that enhancing the unspecific membrane activity of a protein material does not necessarily compromise, but it can even improve, the selective cell targeting offered by an accompanying functional module. Statement of Significance: We have shown here that the combination of cell-penetrating and tumor cell-targeting peptides dramatically enhances precise tumor accumulation of protein-only nanoparticles intended for selective drug delivery, in mouse models of human colorectal cancer. This fact is a step forward for the rational design of multifunctional protein nanomaterials for improved cancer therapies. 22019-01-0120192019-01-01Articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/233714https://dx.doi.org/urn:doi:10.1016/j.actbio.2019.09.002reponame: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 PI18/00650Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 FI16/00017Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2018FI_B2_00051Agència 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-229open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2337142026-06-06T12:50:31Z
dc.title.none.fl_str_mv Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer
title Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer
spellingShingle Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer
Sala, Rita
Protein materials
Self-assembling
Fusogenic peptide
Colorectal cancer
CXCR4
Active targeting
title_short Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer
title_full Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer
title_fullStr Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer
title_full_unstemmed Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer
title_sort Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer
dc.creator.none.fl_str_mv Sala, Rita
Sánchez-García, Laura|||0000-0002-8420-1701
Serna, Naroa|||0000-0001-5682-8198
Céspedes, María Virtudes|||0000-0003-2956-5833
Casanova Rigat, Isolda|||0000-0002-1196-4724
Roldán, Mònica
Sánchez Chardi, Alejandro|||0000-0002-8789-1883
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
Vázquez, Esther|||0000-0003-1052-0424
Mangues, Ramon|||0000-0003-2661-9525
Villaverde, Antonio|||0000-0002-2615-4521
author Sala, Rita
author_facet Sala, Rita
Sánchez-García, Laura|||0000-0002-8420-1701
Serna, Naroa|||0000-0001-5682-8198
Céspedes, María Virtudes|||0000-0003-2956-5833
Casanova Rigat, Isolda|||0000-0002-1196-4724
Roldán, Mònica
Sánchez Chardi, Alejandro|||0000-0002-8789-1883
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
Vázquez, Esther|||0000-0003-1052-0424
Mangues, Ramon|||0000-0003-2661-9525
Villaverde, Antonio|||0000-0002-2615-4521
author_role author
author2 Sánchez-García, Laura|||0000-0002-8420-1701
Serna, Naroa|||0000-0001-5682-8198
Céspedes, María Virtudes|||0000-0003-2956-5833
Casanova Rigat, Isolda|||0000-0002-1196-4724
Roldán, Mònica
Sánchez Chardi, Alejandro|||0000-0002-8789-1883
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
Vázquez, Esther|||0000-0003-1052-0424
Mangues, Ramon|||0000-0003-2661-9525
Villaverde, Antonio|||0000-0002-2615-4521
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Protein materials
Self-assembling
Fusogenic peptide
Colorectal cancer
CXCR4
Active targeting
topic Protein materials
Self-assembling
Fusogenic peptide
Colorectal cancer
CXCR4
Active targeting
description By the appropriate selection of functional peptides and proper accommodation sites, we have generated a set of multifunctional proteins that combine selectivity for CXCR4 cell binding and relevant endosomal escape capabilities linked to the viral peptide HA2. In particular, the construct T22-GFP-HA2-H6 forms nanoparticles that upon administration in mouse models of human, CXCR4 colorectal cancer, accumulates in primary tumor at levels significantly higher than the parental T22-GFP-H6 HA2-lacking version. The in vivo application of a CXCR4 antagonist has confirmed the prevalence of the CXCR4 tumor tissue selectivity over unspecific cell penetration, upon systemic administration of the material. Such specificity is combined with improved endosomal escape, what overall results in a precise and highly efficient tumor biodistribution. These data strongly support the functional recruitment as a convenient approach to generate protein materials for clinical applications. More precisely, they also support the unexpected concept that enhancing the unspecific membrane activity of a protein material does not necessarily compromise, but it can even improve, the selective cell targeting offered by an accompanying functional module. Statement of Significance: We have shown here that the combination of cell-penetrating and tumor cell-targeting peptides dramatically enhances precise tumor accumulation of protein-only nanoparticles intended for selective drug delivery, in mouse models of human colorectal cancer. This fact is a step forward for the rational design of multifunctional protein nanomaterials for improved cancer therapies.
publishDate 2019
dc.date.none.fl_str_mv 2
2019-01-01
2019
2019-01-01
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/233714
https://dx.doi.org/urn:doi:10.1016/j.actbio.2019.09.002
url https://ddd.uab.cat/record/233714
https://dx.doi.org/urn:doi:10.1016/j.actbio.2019.09.002
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 PI18/00650
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 FI16/00017
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2018FI_B2_00051
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
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
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://creativecommons.org/licenses/by-nc-nd/4.0/
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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score 15.301603

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