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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| Format: | Article |
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MDPI AG
2020-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/5/450 |
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| author | Laia Gifre-Renom Estefania Ugarte-Berzal Erik Martens Lise Boon Olivia Cano-Garrido Esther Martínez-Núñez Teresa Luque Ramon Roca-Pinilla Òscar Conchillo-Solé Neus Ferrer-Miralles Antonio Villaverde Ghislain Opdenakker Elena Garcia-Fruitós Anna Arís |
| author_facet | Laia Gifre-Renom Estefania Ugarte-Berzal Erik Martens Lise Boon Olivia Cano-Garrido Esther Martínez-Núñez Teresa Luque Ramon Roca-Pinilla Òscar Conchillo-Solé Neus Ferrer-Miralles Antonio Villaverde Ghislain Opdenakker Elena Garcia-Fruitós Anna Arís |
| author_sort | Laia Gifre-Renom |
| collection | DOAJ |
| 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 <i>mmp9</i> 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. |
| first_indexed | 2024-03-10T19:50:48Z |
| format | Article |
| id | doaj.art-a623558307664d1fa5364f9e6b825c6f |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T19:50:48Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-a623558307664d1fa5364f9e6b825c6f2023-11-20T00:22:30ZengMDPI AGPharmaceutics1999-49232020-05-0112545010.3390/pharmaceutics12050450Recombinant Protein-Based Nanoparticles: Elucidating Their Inflammatory Effects In Vivo and Their Potential as a New Therapeutic FormatLaia Gifre-Renom0Estefania Ugarte-Berzal1Erik Martens2Lise Boon3Olivia Cano-Garrido4Esther Martínez-Núñez5Teresa Luque6Ramon Roca-Pinilla7Òscar Conchillo-Solé8Neus Ferrer-Miralles9Antonio Villaverde10Ghislain Opdenakker11Elena Garcia-Fruitós12Anna Arís13Department of Ruminant Production, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), 08140 Caldes de Montbui, SpainLaboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, University of Leuven, 3000 Leuven, BelgiumLaboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, University of Leuven, 3000 Leuven, BelgiumLaboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, University of Leuven, 3000 Leuven, BelgiumInstitut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, SpainInstitut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, SpainInstitut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, SpainDepartment of Ruminant Production, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), 08140 Caldes de Montbui, SpainInstitut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, SpainInstitut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, SpainInstitut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, SpainLaboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, University of Leuven, 3000 Leuven, BelgiumDepartment of Ruminant Production, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), 08140 Caldes de Montbui, SpainDepartment of Ruminant Production, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), 08140 Caldes de Montbui, SpainBacterial 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 <i>mmp9</i> 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.https://www.mdpi.com/1999-4923/12/5/450inclusion bodymatrix metalloproteinase-9<i>mmp9</i> knock-out micefunctional nanoparticleimmunogenicity |
| spellingShingle | Laia Gifre-Renom Estefania Ugarte-Berzal Erik Martens Lise Boon Olivia Cano-Garrido Esther Martínez-Núñez Teresa Luque Ramon Roca-Pinilla Òscar Conchillo-Solé Neus Ferrer-Miralles Antonio Villaverde Ghislain Opdenakker Elena Garcia-Fruitós Anna Arís Recombinant Protein-Based Nanoparticles: Elucidating Their Inflammatory Effects In Vivo and Their Potential as a New Therapeutic Format Pharmaceutics inclusion body matrix metalloproteinase-9 <i>mmp9</i> knock-out mice functional nanoparticle immunogenicity |
| 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 | inclusion body matrix metalloproteinase-9 <i>mmp9</i> knock-out mice functional nanoparticle immunogenicity |
| url | https://www.mdpi.com/1999-4923/12/5/450 |
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