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...

Full description

Bibliographic Details
Authors: 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
Format: Article
Publication date:2021
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:264010
Online Access:https://ddd.uab.cat/record/264010
https://dx.doi.org/urn:doi:10.1002/adfm.202100914
Access Level:Open access
Keyword:Protein materials
Microparticles
Divalent cations
Secretory granules
Drug release
_version_ 1878741725740007424
author López-Laguna, Hèctor|||0000-0001-5249-8304
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
author_browse Cano-Garrido, Olivia|||0000-0002-5504-2131
López-Laguna, Hèctor|||0000-0001-5249-8304
Mangues, Ramon|||0000-0003-2661-9525
Parladé Molist, Eloi|||0000-0001-5750-550X
Serna, Naroa|||0000-0001-5682-8198
Sánchez Chardi, Alejandro|||0000-0002-8789-1883
Sánchez, Julieta M.|||0000-0001-6676-5776
Sánchez-García, Laura|||0000-0002-8420-1701
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
Villaverde, Antonio|||0000-0002-2615-4521
Voltà-Durán, Eric|||0000-0003-0017-8274
Vázquez, Esther|||0000-0003-1052-0424
Álamo, Patricia|||0000-0003-0510-5701
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
collection Dipòsit Digital de Documents de la UAB
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.
eu_rights_str_mv openAccess
format article
id ES_ea4feb9dbb01de1d1336e5e2a8b05f2e
institution Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
language eng
network_acronym_str ES
network_name_str España
oai_identifier_str oai:ddd.uab.cat:264010
publishDate 2021
publishDateSort 2021
reponame_str Dipòsit Digital de Documents de la UAB
spelling In vitro fabrication of microscale secretory granules 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 Protein materials Microparticles Divalent cations Secretory granules Drug release 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. https://ddd.uab.cat/record/264010 https://dx.doi.org/urn:doi:10.1002/adfm.202100914
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 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_short In vitro fabrication of microscale secretory granules
title_sort In vitro fabrication of microscale secretory granules
topic Protein materials
Microparticles
Divalent cations
Secretory granules
Drug release
topic_facet Protein materials
Microparticles
Divalent cations
Secretory granules
Drug release
url https://ddd.uab.cat/record/264010
https://dx.doi.org/urn:doi:10.1002/adfm.202100914