In vitro fabrication of microscale secretory granules

Advanced medical treatments involving drug delivery require fully biocompatible materials with the ability to release functional drugs in a time-prolonged way. Ideally, the delivered molecules should be self-contained as chemically homogenous entities to prevent the use of potentially toxic scaffold...

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Autores: López-Laguna, Hèctor|||0000-0001-5249-8304, Parladé Molist, Eloi|||0000-0001-5750-550X, Álamo, Patricia|||0000-0003-0510-5701, Sánchez, Julieta M.|||0000-0001-6676-5776, Voltà-Durán, Eric|||0000-0003-0017-8274, Serna, Naroa|||0000-0001-5682-8198, Sánchez-García, Laura|||0000-0002-8420-1701, Cano-Garrido, Olivia|||0000-0002-5504-2131, Sánchez Chardi, Alejandro|||0000-0002-8789-1883, Villaverde, Antonio|||0000-0002-2615-4521, Mangues, Ramon|||0000-0003-2661-9525, Unzueta Elorza, Ugutz|||0000-0001-5119-2266, Vázquez, Esther|||0000-0003-1052-0424
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:264010
Acceso en línea:https://ddd.uab.cat/record/264010
https://dx.doi.org/urn:doi:10.1002/adfm.202100914
Access Level:acceso abierto
Palabra clave:Protein materials
Microparticles
Divalent cations
Secretory granules
Drug release
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spelling In vitro fabrication of microscale secretory granulesLópez-Laguna, Hèctor|||0000-0001-5249-8304Parladé Molist, Eloi|||0000-0001-5750-550XÁlamo, Patricia|||0000-0003-0510-5701Sánchez, Julieta M.|||0000-0001-6676-5776Voltà-Durán, Eric|||0000-0003-0017-8274Serna, Naroa|||0000-0001-5682-8198Sánchez-García, Laura|||0000-0002-8420-1701Cano-Garrido, Olivia|||0000-0002-5504-2131Sánchez Chardi, Alejandro|||0000-0002-8789-1883Villaverde, Antonio|||0000-0002-2615-4521Mangues, Ramon|||0000-0003-2661-9525Unzueta Elorza, Ugutz|||0000-0001-5119-2266Vázquez, Esther|||0000-0003-1052-0424Protein materialsMicroparticlesDivalent cationsSecretory granulesDrug releaseAdvanced medical treatments involving drug delivery require fully biocompatible materials with the ability to release functional drugs in a time-prolonged way. Ideally, the delivered molecules should be self-contained as chemically homogenous entities to prevent the use of potentially toxic scaffolds or hold matrices. In nature, peptidic hormones are self-stored in protein-only secretory granules formed by the reversible coordination of Zn and histidine residues. Inspired by this concept, an in vitro transversal procedure is developed, analyzed, and comparatively applied for the fabrication of protein-only secretory granules at the microscale. These materials can be produced from any polyhistidine-tagged protein using physiological concentrations of Zn as a potent and versatile glue-like agent. The screening of granules formed by 12 engineered and nonengineered proteins at different Zn concentrations revealed optimal fabrication conditions and the consequent release profiles. Moreover, the functional and structural properties of the delivered protein are fully validated using a drug-targeting protein platform in a mouse model of human colorectal cancer. In summary, short histidine tags allow the packaging of structurally and functionally dissimilar polypeptides, which supports the proposed fabrication method as a powerful protocol extensible to diverse clinical scenarios in which slow protein drug delivery is required. 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/264010https://dx.doi.org/urn:doi:10.1002/adfm.202100914reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 BIO2016-76063-RAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-105416RB-I00Instituto 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-229Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CP19/00028Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 FPU18/04615Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2018/FI_B2_00051Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2019/FI_B00352open 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:2640102026-06-06T12:50:31Z
dc.title.none.fl_str_mv In vitro fabrication of microscale secretory granules
title In vitro fabrication of microscale secretory granules
spellingShingle In vitro fabrication of microscale secretory granules
López-Laguna, Hèctor|||0000-0001-5249-8304
Protein materials
Microparticles
Divalent cations
Secretory granules
Drug release
title_short In vitro fabrication of microscale secretory granules
title_full In vitro fabrication of microscale secretory granules
title_fullStr In vitro fabrication of microscale secretory granules
title_full_unstemmed In vitro fabrication of microscale secretory granules
title_sort In vitro fabrication of microscale secretory granules
dc.creator.none.fl_str_mv López-Laguna, Hèctor|||0000-0001-5249-8304
Parladé Molist, Eloi|||0000-0001-5750-550X
Álamo, Patricia|||0000-0003-0510-5701
Sánchez, Julieta M.|||0000-0001-6676-5776
Voltà-Durán, Eric|||0000-0003-0017-8274
Serna, Naroa|||0000-0001-5682-8198
Sánchez-García, Laura|||0000-0002-8420-1701
Cano-Garrido, Olivia|||0000-0002-5504-2131
Sánchez Chardi, Alejandro|||0000-0002-8789-1883
Villaverde, Antonio|||0000-0002-2615-4521
Mangues, Ramon|||0000-0003-2661-9525
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
Vázquez, Esther|||0000-0003-1052-0424
author López-Laguna, Hèctor|||0000-0001-5249-8304
author_facet López-Laguna, Hèctor|||0000-0001-5249-8304
Parladé Molist, Eloi|||0000-0001-5750-550X
Álamo, Patricia|||0000-0003-0510-5701
Sánchez, Julieta M.|||0000-0001-6676-5776
Voltà-Durán, Eric|||0000-0003-0017-8274
Serna, Naroa|||0000-0001-5682-8198
Sánchez-García, Laura|||0000-0002-8420-1701
Cano-Garrido, Olivia|||0000-0002-5504-2131
Sánchez Chardi, Alejandro|||0000-0002-8789-1883
Villaverde, Antonio|||0000-0002-2615-4521
Mangues, Ramon|||0000-0003-2661-9525
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
Vázquez, Esther|||0000-0003-1052-0424
author_role author
author2 Parladé Molist, Eloi|||0000-0001-5750-550X
Álamo, Patricia|||0000-0003-0510-5701
Sánchez, Julieta M.|||0000-0001-6676-5776
Voltà-Durán, Eric|||0000-0003-0017-8274
Serna, Naroa|||0000-0001-5682-8198
Sánchez-García, Laura|||0000-0002-8420-1701
Cano-Garrido, Olivia|||0000-0002-5504-2131
Sánchez Chardi, Alejandro|||0000-0002-8789-1883
Villaverde, Antonio|||0000-0002-2615-4521
Mangues, Ramon|||0000-0003-2661-9525
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
Vázquez, Esther|||0000-0003-1052-0424
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Protein materials
Microparticles
Divalent cations
Secretory granules
Drug release
topic Protein materials
Microparticles
Divalent cations
Secretory granules
Drug release
description Advanced medical treatments involving drug delivery require fully biocompatible materials with the ability to release functional drugs in a time-prolonged way. Ideally, the delivered molecules should be self-contained as chemically homogenous entities to prevent the use of potentially toxic scaffolds or hold matrices. In nature, peptidic hormones are self-stored in protein-only secretory granules formed by the reversible coordination of Zn and histidine residues. Inspired by this concept, an in vitro transversal procedure is developed, analyzed, and comparatively applied for the fabrication of protein-only secretory granules at the microscale. These materials can be produced from any polyhistidine-tagged protein using physiological concentrations of Zn as a potent and versatile glue-like agent. The screening of granules formed by 12 engineered and nonengineered proteins at different Zn concentrations revealed optimal fabrication conditions and the consequent release profiles. Moreover, the functional and structural properties of the delivered protein are fully validated using a drug-targeting protein platform in a mouse model of human colorectal cancer. In summary, short histidine tags allow the packaging of structurally and functionally dissimilar polypeptides, which supports the proposed fabrication method as a powerful protocol extensible to diverse clinical scenarios in which slow protein drug delivery is required.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
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/264010
https://dx.doi.org/urn:doi:10.1002/adfm.202100914
url https://ddd.uab.cat/record/264010
https://dx.doi.org/urn:doi:10.1002/adfm.202100914
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
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-105416RB-I00
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
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CP19/00028
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 FPU18/04615
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2018/FI_B2_00051
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2019/FI_B00352
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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