2026-04-17T17:10:27Zhttps://recercat.cat/oai/request
oai:recercat.cat:2072/4408662024-10-31T05:01:41Zcom_2072_98col_2072_378192
RECERCAT author Gifre-Renom, Laia author Ugarte-Berzal, Estefanía author Martens, Erik author Boon, Lise author Cano-Garrido, Olivia author Martínez-Núñez, Esther author Luque, Teresa author Roca-Pinilla, Ramon author Conchillo-Solé, Oscar author Ferrer-Miralles, Neus author Villaverde Corrales, Antonio author Opdenakker, Ghislain author Garcia-Fruitos, Elena author Arís i Giralt, Anna 2020 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.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. open access 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. https://creativecommons.org/licenses/by/4.0/ Inclusion body Matrix metalloproteinase-9 Mmp9 knock-out mice Functional nanoparticle Immunogenicity Recombinant protein-based nanoparticles : elucidating their inflammatory effects in vivo and their potential as a new therapeutic format Article