Subcutaneous administration of an endocrine-mimetic platform allows for prolonged tumor uptake of a tumor targeting protein

Endocrine-like dynamic protein depots can be fabricated in vitro through the coordination of divalent zinc ions (Zn) with solvent-exposed histidine residues on functional proteins, leading to their controlled aggregation. The resulting microparticles, under physiological conditions, undergo progress...

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Autores: Álamo, Patricia|||0000-0003-0510-5701, López-Laguna, Hèctor|||0000-0001-5249-8304, de Pinho Favaro, Marianna T.|||0000-0003-2942-247X, Gallardo, Alberto|||0000-0002-2514-2027, Alba Castellón, Lorena|||0000-0003-3449-7820, Villaverde, Antonio|||0000-0002-2615-4521, Mangues, Ramon|||0000-0003-2661-9525, Vázquez, Esther|||0000-0003-1052-0424
Tipo de recurso: artículo
Fecha de publicación:2026
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:326190
Acceso en línea:https://ddd.uab.cat/record/326190
https://dx.doi.org/urn:doi:10.1016/j.ijpharm.2026.126585
Access Level:acceso abierto
Palabra clave:Modular protein
Drug delivery
Slow release
Biodistribution
Tumor targeting
Nanoparticles
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spelling Subcutaneous administration of an endocrine-mimetic platform allows for prolonged tumor uptake of a tumor targeting proteinÁlamo, Patricia|||0000-0003-0510-5701López-Laguna, Hèctor|||0000-0001-5249-8304de Pinho Favaro, Marianna T.|||0000-0003-2942-247XGallardo, Alberto|||0000-0002-2514-2027Alba Castellón, Lorena|||0000-0003-3449-7820Villaverde, Antonio|||0000-0002-2615-4521Mangues, Ramon|||0000-0003-2661-9525Vázquez, Esther|||0000-0003-1052-0424Modular proteinDrug deliverySlow releaseBiodistributionTumor targetingNanoparticlesEndocrine-like dynamic protein depots can be fabricated in vitro through the coordination of divalent zinc ions (Zn) with solvent-exposed histidine residues on functional proteins, leading to their controlled aggregation. The resulting microparticles, under physiological conditions, undergo progressive disintegration due to spontaneous Zn dilution, enabling a time-sustained release of the protein components. These chemically pure protein-based materials represent promising drug delivery platforms, with demonstrated efficacy in oncology, vaccinology, tissue regeneration, and antibacterial therapies. To enable systemic delivery of the embedded protein, alternative administration routes are potentially suited, but their effectiveness in terms of biodistribution and accumulation in target tissues remains unexplored. Using a CXCR4 cancer mouse model, we investigated the tumor targeting and permanence of a self-assembling, CXCR4-binding fluorescent protein administered in the form of secretory granules via subcutaneous, intramuscular, or intraperitoneal injection. Our data reveal that subcutaneous administration supports prolonged protein retention at the injection site, its release within the local draining lymphatic vessels, extended circulation time, and significantly higher tumor accumulation 10 days post-injection. Compared to intramuscular and intraperitoneal routes, the subcutaneous pathway presents clear advantages, potentially allowing reduced dosing frequency in protein-based therapies aimed at maintaining steady systemic and target tissue levels. 22026-01-0120262026-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/326190https://dx.doi.org/urn:doi:10.1016/j.ijpharm.2026.126585reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2022-1368450OB-10Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-105416RB-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PDC2022-133858-I00Generalitat de Catalunya https://doi.org/10.13039/501100002809 2021/SGR-00092Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI24/01476Ministerio de Sanidad y Consumo CB06/01/0014Ministerio de Sanidad y Consumo CB06/01/1031Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CP24/00111open 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:3261902026-06-06T12:50:31Z
dc.title.none.fl_str_mv Subcutaneous administration of an endocrine-mimetic platform allows for prolonged tumor uptake of a tumor targeting protein
title Subcutaneous administration of an endocrine-mimetic platform allows for prolonged tumor uptake of a tumor targeting protein
spellingShingle Subcutaneous administration of an endocrine-mimetic platform allows for prolonged tumor uptake of a tumor targeting protein
Álamo, Patricia|||0000-0003-0510-5701
Modular protein
Drug delivery
Slow release
Biodistribution
Tumor targeting
Nanoparticles
title_short Subcutaneous administration of an endocrine-mimetic platform allows for prolonged tumor uptake of a tumor targeting protein
title_full Subcutaneous administration of an endocrine-mimetic platform allows for prolonged tumor uptake of a tumor targeting protein
title_fullStr Subcutaneous administration of an endocrine-mimetic platform allows for prolonged tumor uptake of a tumor targeting protein
title_full_unstemmed Subcutaneous administration of an endocrine-mimetic platform allows for prolonged tumor uptake of a tumor targeting protein
title_sort Subcutaneous administration of an endocrine-mimetic platform allows for prolonged tumor uptake of a tumor targeting protein
dc.creator.none.fl_str_mv Álamo, Patricia|||0000-0003-0510-5701
López-Laguna, Hèctor|||0000-0001-5249-8304
de Pinho Favaro, Marianna T.|||0000-0003-2942-247X
Gallardo, Alberto|||0000-0002-2514-2027
Alba Castellón, Lorena|||0000-0003-3449-7820
Villaverde, Antonio|||0000-0002-2615-4521
Mangues, Ramon|||0000-0003-2661-9525
Vázquez, Esther|||0000-0003-1052-0424
author Álamo, Patricia|||0000-0003-0510-5701
author_facet Álamo, Patricia|||0000-0003-0510-5701
López-Laguna, Hèctor|||0000-0001-5249-8304
de Pinho Favaro, Marianna T.|||0000-0003-2942-247X
Gallardo, Alberto|||0000-0002-2514-2027
Alba Castellón, Lorena|||0000-0003-3449-7820
Villaverde, Antonio|||0000-0002-2615-4521
Mangues, Ramon|||0000-0003-2661-9525
Vázquez, Esther|||0000-0003-1052-0424
author_role author
author2 López-Laguna, Hèctor|||0000-0001-5249-8304
de Pinho Favaro, Marianna T.|||0000-0003-2942-247X
Gallardo, Alberto|||0000-0002-2514-2027
Alba Castellón, Lorena|||0000-0003-3449-7820
Villaverde, Antonio|||0000-0002-2615-4521
Mangues, Ramon|||0000-0003-2661-9525
Vázquez, Esther|||0000-0003-1052-0424
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Modular protein
Drug delivery
Slow release
Biodistribution
Tumor targeting
Nanoparticles
topic Modular protein
Drug delivery
Slow release
Biodistribution
Tumor targeting
Nanoparticles
description Endocrine-like dynamic protein depots can be fabricated in vitro through the coordination of divalent zinc ions (Zn) with solvent-exposed histidine residues on functional proteins, leading to their controlled aggregation. The resulting microparticles, under physiological conditions, undergo progressive disintegration due to spontaneous Zn dilution, enabling a time-sustained release of the protein components. These chemically pure protein-based materials represent promising drug delivery platforms, with demonstrated efficacy in oncology, vaccinology, tissue regeneration, and antibacterial therapies. To enable systemic delivery of the embedded protein, alternative administration routes are potentially suited, but their effectiveness in terms of biodistribution and accumulation in target tissues remains unexplored. Using a CXCR4 cancer mouse model, we investigated the tumor targeting and permanence of a self-assembling, CXCR4-binding fluorescent protein administered in the form of secretory granules via subcutaneous, intramuscular, or intraperitoneal injection. Our data reveal that subcutaneous administration supports prolonged protein retention at the injection site, its release within the local draining lymphatic vessels, extended circulation time, and significantly higher tumor accumulation 10 days post-injection. Compared to intramuscular and intraperitoneal routes, the subcutaneous pathway presents clear advantages, potentially allowing reduced dosing frequency in protein-based therapies aimed at maintaining steady systemic and target tissue levels.
publishDate 2026
dc.date.none.fl_str_mv 2
2026-01-01
2026
2026-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/326190
https://dx.doi.org/urn:doi:10.1016/j.ijpharm.2026.126585
url https://ddd.uab.cat/record/326190
https://dx.doi.org/urn:doi:10.1016/j.ijpharm.2026.126585
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 PID2022-1368450OB-10
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-105416RB-I00
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PDC2022-133858-I00
Generalitat de Catalunya https://doi.org/10.13039/501100002809 2021/SGR-00092
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI24/01476
Ministerio de Sanidad y Consumo CB06/01/0014
Ministerio de Sanidad y Consumo CB06/01/1031
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CP24/00111
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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