Recombinant protein-based nanoparticles : elucidating their inflammatory effects in vivo and their potential as a new therapeutic format
Gifre-Renom, Laia (Institut de Recerca i Tecnologia Agroalimentàries)
Ugarte-Berzal, Estefanía (Katholieke Universiteit Leuven. Department of Microbiology, Immunology and Transplantation)
Martens, Erik (Katholieke Universiteit Leuven. Department of Microbiology, Immunology and Transplantation)
Boon, Lise (Katholieke Universiteit Leuven. Department of Microbiology, Immunology and Transplantation)
Cano-Garrido, Olivia (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Martínez-Núñez, Esther (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Luque, Teresa (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Roca-Pinilla, Ramon (Institut de Recerca i Tecnologia Agroalimentàries)
Conchillo-Solé, Oscar (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Ferrer-Miralles, Neus (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Villaverde Corrales, Antonio (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Opdenakker, Ghislain (Katholieke Universiteit Leuven. Department of Microbiology, Immunology and Transplantation)
Garcia-Fruitos, Elena (Institut de Recerca i Tecnologia Agroalimentàries)
Arís i Giralt, Anna (Institut de Recerca i Tecnologia Agroalimentàries)

Fecha:	2020
Resumen:	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.
Ayudas:	Ministerio de Economía y Competitividad RTA2015-00064-C02 Ministerio de Economía y Competitividad RTA2012-00028-C02
Nota:	Altres ajuts: we are also indebted to CERCA Programme (Generalitat de Catalunya) and European Social Fund for supporting our research. L.G.-R. received a pre-doctoral fellowship from INIA (FPI-INIA, MINECO), R.R.-P. from AGAUR (FI-AGAUR), and O.C.-G. from MECD (FPU). E.G.-F. received a post-doctoral fellowship from INIA (DOC-INIA) and A.V. an ICREA Academia award.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Inclusion body ; Matrix metalloproteinase-9 ; Mmp9 knock-out mice ; Functional nanoparticle ; Immunogenicity
Publicado en:	Pharmaceutics, Vol. 12, issue 5 (2020) , art. 450, ISSN 1999-4923

DOI: 10.3390/pharmaceutics12050450
PMID: 32414218

13 p, 1.9 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Instituto de Biotecnología y de Biomedicina (IBB)
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