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Recombinant Protein-Based Nanoparticles: Elucidating Their Inflammatory Effects In Vivo and Their Potential as a New Therapeutic Format

Bacterial inclusion bodies (IBs) are protein-based nanoparticles of a few hundred nanometers formed during recombinant protein production processes in different bacterial hosts. IBs contain active protein in a mechanically stable nanostructured format that has been broadly characterized, showing pro...

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Autores principales: Gifre-Renom, Laia, Ugarte-Berzal, Estefania, Martens, Erik, Boon, Lise, Cano-Garrido, Olivia, Martínez-Núñez, Esther, Luque, Teresa, Roca-Pinilla, Ramon, Conchillo-Solé, Òscar, Ferrer-Miralles, Neus, Villaverde, Antonio, Opdenakker, Ghislain, Garcia-Fruitós, Elena, Arís, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284881/
https://www.ncbi.nlm.nih.gov/pubmed/32414218
http://dx.doi.org/10.3390/pharmaceutics12050450
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author Gifre-Renom, Laia
Ugarte-Berzal, Estefania
Martens, Erik
Boon, Lise
Cano-Garrido, Olivia
Martínez-Núñez, Esther
Luque, Teresa
Roca-Pinilla, Ramon
Conchillo-Solé, Òscar
Ferrer-Miralles, Neus
Villaverde, Antonio
Opdenakker, Ghislain
Garcia-Fruitós, Elena
Arís, Anna
author_facet Gifre-Renom, Laia
Ugarte-Berzal, Estefania
Martens, Erik
Boon, Lise
Cano-Garrido, Olivia
Martínez-Núñez, Esther
Luque, Teresa
Roca-Pinilla, Ramon
Conchillo-Solé, Òscar
Ferrer-Miralles, Neus
Villaverde, Antonio
Opdenakker, Ghislain
Garcia-Fruitós, Elena
Arís, Anna
author_sort Gifre-Renom, Laia
collection PubMed
description Bacterial inclusion bodies (IBs) are protein-based nanoparticles of a few hundred nanometers formed during recombinant protein production processes in different bacterial hosts. IBs contain active protein in a mechanically stable nanostructured format that has been broadly characterized, showing promising potential in different fields such as tissue engineering, protein replacement therapies, cancer, and biotechnology. For immunomodulatory purposes, however, the interference of the format immunogenic properties—intrinsic to IBs—with the specific effects of the therapeutic protein is still an uncovered gap. For that, active and inactive forms of the catalytic domain of a matrix metalloproteinase-9 (MMP-9 and mutMMP-9, respectively) have been produced as IBs and compared with the soluble form for dermal inflammatory effects in mmp9 knock-out mice. After protein injections in air-pouches in the mouse model, MMP-9 IBs induce local neutrophil recruitment and increase pro-inflammatory chemokine levels, lasting for at least two days, whereas the effects triggered by the soluble MMP-9 format fade out after 3 h. Interestingly, the IB intrinsic effects (mutMMP-9 IBs) do not last more than 24 h. Therefore, it may be concluded that IBs could be used for the delivery of therapeutic proteins, such as immunomodulating proteins while preserving their stability in the specific tissue and without triggering important unspecific inflammatory responses due to the protein format.
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spelling pubmed-72848812020-06-17 Recombinant Protein-Based Nanoparticles: Elucidating Their Inflammatory Effects In Vivo and Their Potential as a New Therapeutic Format Gifre-Renom, Laia Ugarte-Berzal, Estefania Martens, Erik Boon, Lise Cano-Garrido, Olivia Martínez-Núñez, Esther Luque, Teresa Roca-Pinilla, Ramon Conchillo-Solé, Òscar Ferrer-Miralles, Neus Villaverde, Antonio Opdenakker, Ghislain Garcia-Fruitós, Elena Arís, Anna Pharmaceutics Article Bacterial inclusion bodies (IBs) are protein-based nanoparticles of a few hundred nanometers formed during recombinant protein production processes in different bacterial hosts. IBs contain active protein in a mechanically stable nanostructured format that has been broadly characterized, showing promising potential in different fields such as tissue engineering, protein replacement therapies, cancer, and biotechnology. For immunomodulatory purposes, however, the interference of the format immunogenic properties—intrinsic to IBs—with the specific effects of the therapeutic protein is still an uncovered gap. For that, active and inactive forms of the catalytic domain of a matrix metalloproteinase-9 (MMP-9 and mutMMP-9, respectively) have been produced as IBs and compared with the soluble form for dermal inflammatory effects in mmp9 knock-out mice. After protein injections in air-pouches in the mouse model, MMP-9 IBs induce local neutrophil recruitment and increase pro-inflammatory chemokine levels, lasting for at least two days, whereas the effects triggered by the soluble MMP-9 format fade out after 3 h. Interestingly, the IB intrinsic effects (mutMMP-9 IBs) do not last more than 24 h. Therefore, it may be concluded that IBs could be used for the delivery of therapeutic proteins, such as immunomodulating proteins while preserving their stability in the specific tissue and without triggering important unspecific inflammatory responses due to the protein format. MDPI 2020-05-13 /pmc/articles/PMC7284881/ /pubmed/32414218 http://dx.doi.org/10.3390/pharmaceutics12050450 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gifre-Renom, Laia
Ugarte-Berzal, Estefania
Martens, Erik
Boon, Lise
Cano-Garrido, Olivia
Martínez-Núñez, Esther
Luque, Teresa
Roca-Pinilla, Ramon
Conchillo-Solé, Òscar
Ferrer-Miralles, Neus
Villaverde, Antonio
Opdenakker, Ghislain
Garcia-Fruitós, Elena
Arís, Anna
Recombinant Protein-Based Nanoparticles: Elucidating Their Inflammatory Effects In Vivo and Their Potential as a New Therapeutic Format
title Recombinant Protein-Based Nanoparticles: Elucidating Their Inflammatory Effects In Vivo and Their Potential as a New Therapeutic Format
title_full Recombinant Protein-Based Nanoparticles: Elucidating Their Inflammatory Effects In Vivo and Their Potential as a New Therapeutic Format
title_fullStr Recombinant Protein-Based Nanoparticles: Elucidating Their Inflammatory Effects In Vivo and Their Potential as a New Therapeutic Format
title_full_unstemmed Recombinant Protein-Based Nanoparticles: Elucidating Their Inflammatory Effects In Vivo and Their Potential as a New Therapeutic Format
title_short Recombinant Protein-Based Nanoparticles: Elucidating Their Inflammatory Effects In Vivo and Their Potential as a New Therapeutic Format
title_sort recombinant protein-based nanoparticles: elucidating their inflammatory effects in vivo and their potential as a new therapeutic format
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284881/
https://www.ncbi.nlm.nih.gov/pubmed/32414218
http://dx.doi.org/10.3390/pharmaceutics12050450
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