Engineering non-antibody human proteins as efficient scaffolds for selective, receptor-targeted drug delivery

Self-assembling non-immunoglobulin scaffold proteins are a promising class of nanoscale carriers for drug delivery and interesting alternatives to antibody-based carriers that are not sufficiently efficient in systemic administration. To exploit their potentialities in clinics, protein scaffolds nee...

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Autores: Serna, Naroa|||0000-0001-5682-8198, Pallarès, Victor|||0000-0002-9851-0345, Unzueta Elorza, Ugutz|||0000-0001-5119-2266, Garcia León, Annabel|||0000-0003-3007-9306, Voltà-Durán, Eric|||0000-0003-0017-8274, Sánchez Chardi, Alejandro|||0000-0002-8789-1883, Parladé Molist, Eloi|||0000-0001-5750-550X, Rueda, Ariana|||0000-0001-7588-9279, Casanova Rigat, Isolda|||0000-0002-1196-4724, Falgàs, Aïda|||0000-0002-5040-2265, Alba Castellón, Lorena|||0000-0003-3449-7820, Sierra, Jorge|||0000-0002-7966-0356, Villaverde, Antonio|||0000-0002-2615-4521, Vázquez, Esther|||0000-0003-1052-0424, Mangues, Ramon|||0000-0003-2661-9525
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:251876
Acceso en línea:https://ddd.uab.cat/record/251876
https://dx.doi.org/urn:doi:10.1016/j.jconrel.2022.01.017
Access Level:acceso abierto
Palabra clave:Scaffold proteins
Self-assembling
Nanoparticles
Drug delivery
Biomaterials
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spelling Engineering non-antibody human proteins as efficient scaffolds for selective, receptor-targeted drug deliverySerna, Naroa|||0000-0001-5682-8198Pallarès, Victor|||0000-0002-9851-0345Unzueta Elorza, Ugutz|||0000-0001-5119-2266Garcia León, Annabel|||0000-0003-3007-9306Voltà-Durán, Eric|||0000-0003-0017-8274Sánchez Chardi, Alejandro|||0000-0002-8789-1883Parladé Molist, Eloi|||0000-0001-5750-550XRueda, Ariana|||0000-0001-7588-9279Casanova Rigat, Isolda|||0000-0002-1196-4724Falgàs, Aïda|||0000-0002-5040-2265Alba Castellón, Lorena|||0000-0003-3449-7820Sierra, Jorge|||0000-0002-7966-0356Villaverde, Antonio|||0000-0002-2615-4521Vázquez, Esther|||0000-0003-1052-0424Mangues, Ramon|||0000-0003-2661-9525Scaffold proteinsSelf-assemblingNanoparticlesDrug deliveryBiomaterialsSelf-assembling non-immunoglobulin scaffold proteins are a promising class of nanoscale carriers for drug delivery and interesting alternatives to antibody-based carriers that are not sufficiently efficient in systemic administration. To exploit their potentialities in clinics, protein scaffolds need to be further tailored to confer appropriate targeting and to overcome their potential immunogenicity, short half-life in plasma and proteolytic degradation. We have here engineered three human scaffold proteins as drug carrier nanoparticles to target the cytokine receptor CXCR4, a tumoral cell surface marker of high clinical relevance. The capability of these scaffolds for the selective delivery of Monomethyl auristatin E has been comparatively evaluated in a disseminated mouse model of human, CXCR4+ acute myeloid leukemia. Monomethyl auristatin E is an ultra-potent anti-mitotic drug used against a range of hematological neoplasias, which because of its high toxicity is not currently administered as a free drug but as payload in antibody-drug conjugates. The protein nanoconjugates generated here offer a collective strength of simple manufacturing process, high proteolytic and structural stability and multivalent ligand receptor interactions that result in a highly efficient and selective delivery of the payload drug and in a potent anticancer effect. The approach shown here stresses this class of human scaffold proteins as promising alternatives to antibodies for targeted drug delivery in the rapidly evolving drug development landscape. 22022-01-0120222022-01-01Articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/251876https://dx.doi.org/urn:doi:10.1016/j.jconrel.2022.01.017reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-105416RB-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 BIO2016-76063-RAgència 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 2017/SGR-1395Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-865Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00650Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI20/00400Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTC-2017-6125-1Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 FPU18/04615Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CP19/00028open 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:2518762026-06-06T12:50:31Z
dc.title.none.fl_str_mv Engineering non-antibody human proteins as efficient scaffolds for selective, receptor-targeted drug delivery
title Engineering non-antibody human proteins as efficient scaffolds for selective, receptor-targeted drug delivery
spellingShingle Engineering non-antibody human proteins as efficient scaffolds for selective, receptor-targeted drug delivery
Serna, Naroa|||0000-0001-5682-8198
Scaffold proteins
Self-assembling
Nanoparticles
Drug delivery
Biomaterials
title_short Engineering non-antibody human proteins as efficient scaffolds for selective, receptor-targeted drug delivery
title_full Engineering non-antibody human proteins as efficient scaffolds for selective, receptor-targeted drug delivery
title_fullStr Engineering non-antibody human proteins as efficient scaffolds for selective, receptor-targeted drug delivery
title_full_unstemmed Engineering non-antibody human proteins as efficient scaffolds for selective, receptor-targeted drug delivery
title_sort Engineering non-antibody human proteins as efficient scaffolds for selective, receptor-targeted drug delivery
dc.creator.none.fl_str_mv Serna, Naroa|||0000-0001-5682-8198
Pallarès, Victor|||0000-0002-9851-0345
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
Garcia León, Annabel|||0000-0003-3007-9306
Voltà-Durán, Eric|||0000-0003-0017-8274
Sánchez Chardi, Alejandro|||0000-0002-8789-1883
Parladé Molist, Eloi|||0000-0001-5750-550X
Rueda, Ariana|||0000-0001-7588-9279
Casanova Rigat, Isolda|||0000-0002-1196-4724
Falgàs, Aïda|||0000-0002-5040-2265
Alba Castellón, Lorena|||0000-0003-3449-7820
Sierra, Jorge|||0000-0002-7966-0356
Villaverde, Antonio|||0000-0002-2615-4521
Vázquez, Esther|||0000-0003-1052-0424
Mangues, Ramon|||0000-0003-2661-9525
author Serna, Naroa|||0000-0001-5682-8198
author_facet Serna, Naroa|||0000-0001-5682-8198
Pallarès, Victor|||0000-0002-9851-0345
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
Garcia León, Annabel|||0000-0003-3007-9306
Voltà-Durán, Eric|||0000-0003-0017-8274
Sánchez Chardi, Alejandro|||0000-0002-8789-1883
Parladé Molist, Eloi|||0000-0001-5750-550X
Rueda, Ariana|||0000-0001-7588-9279
Casanova Rigat, Isolda|||0000-0002-1196-4724
Falgàs, Aïda|||0000-0002-5040-2265
Alba Castellón, Lorena|||0000-0003-3449-7820
Sierra, Jorge|||0000-0002-7966-0356
Villaverde, Antonio|||0000-0002-2615-4521
Vázquez, Esther|||0000-0003-1052-0424
Mangues, Ramon|||0000-0003-2661-9525
author_role author
author2 Pallarès, Victor|||0000-0002-9851-0345
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
Garcia León, Annabel|||0000-0003-3007-9306
Voltà-Durán, Eric|||0000-0003-0017-8274
Sánchez Chardi, Alejandro|||0000-0002-8789-1883
Parladé Molist, Eloi|||0000-0001-5750-550X
Rueda, Ariana|||0000-0001-7588-9279
Casanova Rigat, Isolda|||0000-0002-1196-4724
Falgàs, Aïda|||0000-0002-5040-2265
Alba Castellón, Lorena|||0000-0003-3449-7820
Sierra, Jorge|||0000-0002-7966-0356
Villaverde, Antonio|||0000-0002-2615-4521
Vázquez, Esther|||0000-0003-1052-0424
Mangues, Ramon|||0000-0003-2661-9525
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Scaffold proteins
Self-assembling
Nanoparticles
Drug delivery
Biomaterials
topic Scaffold proteins
Self-assembling
Nanoparticles
Drug delivery
Biomaterials
description Self-assembling non-immunoglobulin scaffold proteins are a promising class of nanoscale carriers for drug delivery and interesting alternatives to antibody-based carriers that are not sufficiently efficient in systemic administration. To exploit their potentialities in clinics, protein scaffolds need to be further tailored to confer appropriate targeting and to overcome their potential immunogenicity, short half-life in plasma and proteolytic degradation. We have here engineered three human scaffold proteins as drug carrier nanoparticles to target the cytokine receptor CXCR4, a tumoral cell surface marker of high clinical relevance. The capability of these scaffolds for the selective delivery of Monomethyl auristatin E has been comparatively evaluated in a disseminated mouse model of human, CXCR4+ acute myeloid leukemia. Monomethyl auristatin E is an ultra-potent anti-mitotic drug used against a range of hematological neoplasias, which because of its high toxicity is not currently administered as a free drug but as payload in antibody-drug conjugates. The protein nanoconjugates generated here offer a collective strength of simple manufacturing process, high proteolytic and structural stability and multivalent ligand receptor interactions that result in a highly efficient and selective delivery of the payload drug and in a potent anticancer effect. The approach shown here stresses this class of human scaffold proteins as promising alternatives to antibodies for targeted drug delivery in the rapidly evolving drug development landscape.
publishDate 2022
dc.date.none.fl_str_mv 2
2022-01-01
2022
2022-01-01
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/251876
https://dx.doi.org/urn:doi:10.1016/j.jconrel.2022.01.017
url https://ddd.uab.cat/record/251876
https://dx.doi.org/urn:doi:10.1016/j.jconrel.2022.01.017
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 PID2019-105416RB-I00
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 BIO2016-76063-R
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 2017/SGR-1395
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-865
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00650
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI20/00400
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTC-2017-6125-1
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 FPU18/04615
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CP19/00028
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
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