Tailored PGE2 Immunomodulation of moDCs by Nano-Encapsulated EP2/EP4 Antagonists
Prostaglandin E2 (PGE2) is an important maturation mediator for dendritic cells (DCs). However, increased PGE2 levels in the tumor exert immunosuppressive effects on DCs by signaling through two E-Prostanoid (EP) receptors: EP2 and EP4. Blocking EP-receptor signaling of PGE2 with antagonists is curr...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/1392 |
| _version_ | 1797441386600988672 |
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| author | Johanna Bödder Leanne M. Kok Jonathan A. Fauerbach Georgina Flórez-Grau I. Jolanda M. de Vries |
| author_facet | Johanna Bödder Leanne M. Kok Jonathan A. Fauerbach Georgina Flórez-Grau I. Jolanda M. de Vries |
| author_sort | Johanna Bödder |
| collection | DOAJ |
| description | Prostaglandin E2 (PGE2) is an important maturation mediator for dendritic cells (DCs). However, increased PGE2 levels in the tumor exert immunosuppressive effects on DCs by signaling through two E-Prostanoid (EP) receptors: EP2 and EP4. Blocking EP-receptor signaling of PGE2 with antagonists is currently being investigated for clinical applications to enhance anti-tumor immunity. In this study, we investigated a new delivery approach by encapsulating EP2/EP4 antagonists in polymeric nanoparticles. The nanoparticles were characterized for size, antagonist loading, and release. The efficacy of the encapsulated antagonists to block PGE2 signaling was analyzed using monocyte-derived DCs (moDCs). The obtained nanoparticles were sized between 210 and 260 nm. The encapsulation efficacy of the EP2/EP4 antagonists was 20% and 17%, respectively, and was further increased with the co-encapsulation of both antagonists. The treatment of moDCs with co-encapsulation EP2/EP4 antagonists prevented PGE2-induced co-stimulatory marker expression. Even though both antagonists showed a burst release within 15 min at 37 °C, the nanoparticles executed the immunomodulatory effects on moDCs. In summary, we demonstrate the functionality of EP2/EP4 antagonist-loaded nanoparticles to overcome PGE2 modulation of moDCs. |
| first_indexed | 2024-03-09T12:22:18Z |
| format | Article |
| id | doaj.art-ec8c8729468e440c862a4212bf76cfad |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:22:18Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ec8c8729468e440c862a4212bf76cfad2023-11-30T22:39:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242139210.3390/ijms24021392Tailored PGE2 Immunomodulation of moDCs by Nano-Encapsulated EP2/EP4 AntagonistsJohanna Bödder0Leanne M. Kok1Jonathan A. Fauerbach2Georgina Flórez-Grau3I. Jolanda M. de Vries4Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsR&D Reagents, Chemical Biology Department, Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, GermanyDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsProstaglandin E2 (PGE2) is an important maturation mediator for dendritic cells (DCs). However, increased PGE2 levels in the tumor exert immunosuppressive effects on DCs by signaling through two E-Prostanoid (EP) receptors: EP2 and EP4. Blocking EP-receptor signaling of PGE2 with antagonists is currently being investigated for clinical applications to enhance anti-tumor immunity. In this study, we investigated a new delivery approach by encapsulating EP2/EP4 antagonists in polymeric nanoparticles. The nanoparticles were characterized for size, antagonist loading, and release. The efficacy of the encapsulated antagonists to block PGE2 signaling was analyzed using monocyte-derived DCs (moDCs). The obtained nanoparticles were sized between 210 and 260 nm. The encapsulation efficacy of the EP2/EP4 antagonists was 20% and 17%, respectively, and was further increased with the co-encapsulation of both antagonists. The treatment of moDCs with co-encapsulation EP2/EP4 antagonists prevented PGE2-induced co-stimulatory marker expression. Even though both antagonists showed a burst release within 15 min at 37 °C, the nanoparticles executed the immunomodulatory effects on moDCs. In summary, we demonstrate the functionality of EP2/EP4 antagonist-loaded nanoparticles to overcome PGE2 modulation of moDCs.https://www.mdpi.com/1422-0067/24/2/1392prostaglandin E2EP2/EP4 antagonistdendritic cellsnanoparticlesdelivery |
| spellingShingle | Johanna Bödder Leanne M. Kok Jonathan A. Fauerbach Georgina Flórez-Grau I. Jolanda M. de Vries Tailored PGE2 Immunomodulation of moDCs by Nano-Encapsulated EP2/EP4 Antagonists International Journal of Molecular Sciences prostaglandin E2 EP2/EP4 antagonist dendritic cells nanoparticles delivery |
| title | Tailored PGE2 Immunomodulation of moDCs by Nano-Encapsulated EP2/EP4 Antagonists |
| title_full | Tailored PGE2 Immunomodulation of moDCs by Nano-Encapsulated EP2/EP4 Antagonists |
| title_fullStr | Tailored PGE2 Immunomodulation of moDCs by Nano-Encapsulated EP2/EP4 Antagonists |
| title_full_unstemmed | Tailored PGE2 Immunomodulation of moDCs by Nano-Encapsulated EP2/EP4 Antagonists |
| title_short | Tailored PGE2 Immunomodulation of moDCs by Nano-Encapsulated EP2/EP4 Antagonists |
| title_sort | tailored pge2 immunomodulation of modcs by nano encapsulated ep2 ep4 antagonists |
| topic | prostaglandin E2 EP2/EP4 antagonist dendritic cells nanoparticles delivery |
| url | https://www.mdpi.com/1422-0067/24/2/1392 |
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