Poly(methyl vinyl ether-co-maleic anhydride) nanoparticles as innate immune system activators
Adjuvant research is being oriented to TLR-agonists, but complement activation has been relatively unexplored. In previous studies it was demonstrated that poly(methyl vinyl ether-co-maleic anhydride) nanoparticles (PVMA NPs) used as adjuvant differentially activate dendritic cells through toll like...
| Main Authors: | , , , , , , , , |
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
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Elsevier
2011
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10171/20362 |
| _version_ | 1793400146427379712 |
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| author | Camacho, A.I. (A.I.) Raquel Tamayo, I. (Ibai) Souza, J. (Juliana) de Lasarte, J.J. (Juan José) Mansilla, C. (Cristina) Esparza, I. (Irene) Irache, J.M. (Juan Manuel) Gamazo, C. (Carlos) |
| author_facet | Camacho, A.I. (A.I.) Raquel Tamayo, I. (Ibai) Souza, J. (Juliana) de Lasarte, J.J. (Juan José) Mansilla, C. (Cristina) Esparza, I. (Irene) Irache, J.M. (Juan Manuel) Gamazo, C. (Carlos) |
| author_sort | Camacho, A.I. (A.I.) |
| collection | DSpace |
| description | Adjuvant research is being oriented to TLR-agonists, but complement activation has been relatively unexplored. In previous studies it was demonstrated that poly(methyl vinyl ether-co-maleic anhydride) nanoparticles (PVMA NPs) used as adjuvant differentially activate dendritic cells through toll like receptors (TLR) stimulation, however, a high dose of these NPs was used. Now, we demonstrated a dose-response effect, with a concentration as low as 20μg/mL able to stimulate TLR2 and TLR4 transfected dendritic cells. In addition, we investigated whether PVMA NPs are able to exploit also the immunomodulatory benefits of complement activation. Results indicated that the hydroxylated surface of these NPs highly activated the complement cascade, as measured by adsorption studies and a complement fixation bioassay. Stable binding of C3b to NPs was confirmed as indicated by lability to SDS treatment after washing resistance. Complement consumption was confirmed as the lytic capacity of complement exposed to NPs was abolished against antibody-sensitized sheep erythrocytes, with a minimal inhibitory concentration of 50μg NPs, equivalent to a surface of 1cm(2). On the contrary, nanoparticles prepared with poly(lactic-co-glycolic acid) (PLGA), used as a reference, did not consume complement at a concentration ≥3mg NPs (≥40cm(2)). Complement consumption was inhibited when PVMA NPs were cross-linked with diamino groups (1,3-diaminopropane), indicating the role of hydroxyl groups as responsible of the phenomenon. These results favour a model whereby PVMA NPs adjuvant activate complement on site to attract immature antigen presenting cells that are activated through TLR2 and TLR4. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-20362 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2011 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-203622022-11-28T11:33:53Z Poly(methyl vinyl ether-co-maleic anhydride) nanoparticles as innate immune system activators Camacho, A.I. (A.I.) Raquel Tamayo, I. (Ibai) Souza, J. (Juliana) de Lasarte, J.J. (Juan José) Mansilla, C. (Cristina) Esparza, I. (Irene) Irache, J.M. (Juan Manuel) Gamazo, C. (Carlos) Nanoparticles Adjuvant TLR- agonist Complement activation Adjuvant research is being oriented to TLR-agonists, but complement activation has been relatively unexplored. In previous studies it was demonstrated that poly(methyl vinyl ether-co-maleic anhydride) nanoparticles (PVMA NPs) used as adjuvant differentially activate dendritic cells through toll like receptors (TLR) stimulation, however, a high dose of these NPs was used. Now, we demonstrated a dose-response effect, with a concentration as low as 20μg/mL able to stimulate TLR2 and TLR4 transfected dendritic cells. In addition, we investigated whether PVMA NPs are able to exploit also the immunomodulatory benefits of complement activation. Results indicated that the hydroxylated surface of these NPs highly activated the complement cascade, as measured by adsorption studies and a complement fixation bioassay. Stable binding of C3b to NPs was confirmed as indicated by lability to SDS treatment after washing resistance. Complement consumption was confirmed as the lytic capacity of complement exposed to NPs was abolished against antibody-sensitized sheep erythrocytes, with a minimal inhibitory concentration of 50μg NPs, equivalent to a surface of 1cm(2). On the contrary, nanoparticles prepared with poly(lactic-co-glycolic acid) (PLGA), used as a reference, did not consume complement at a concentration ≥3mg NPs (≥40cm(2)). Complement consumption was inhibited when PVMA NPs were cross-linked with diamino groups (1,3-diaminopropane), indicating the role of hydroxyl groups as responsible of the phenomenon. These results favour a model whereby PVMA NPs adjuvant activate complement on site to attract immature antigen presenting cells that are activated through TLR2 and TLR4. 2011-12-22T13:52:45Z 2011-12-22T13:52:45Z 2011 info:eu-repo/semantics/article https://hdl.handle.net/10171/20362 eng info:eu-repo/semantics/openAccess application/pdf Elsevier |
| spellingShingle | Nanoparticles Adjuvant TLR- agonist Complement activation Camacho, A.I. (A.I.) Raquel Tamayo, I. (Ibai) Souza, J. (Juliana) de Lasarte, J.J. (Juan José) Mansilla, C. (Cristina) Esparza, I. (Irene) Irache, J.M. (Juan Manuel) Gamazo, C. (Carlos) Poly(methyl vinyl ether-co-maleic anhydride) nanoparticles as innate immune system activators |
| title | Poly(methyl vinyl ether-co-maleic anhydride) nanoparticles as innate immune system activators |
| title_full | Poly(methyl vinyl ether-co-maleic anhydride) nanoparticles as innate immune system activators |
| title_fullStr | Poly(methyl vinyl ether-co-maleic anhydride) nanoparticles as innate immune system activators |
| title_full_unstemmed | Poly(methyl vinyl ether-co-maleic anhydride) nanoparticles as innate immune system activators |
| title_short | Poly(methyl vinyl ether-co-maleic anhydride) nanoparticles as innate immune system activators |
| title_sort | poly(methyl vinyl ether-co-maleic anhydride) nanoparticles as innate immune system activators |
| topic | Nanoparticles Adjuvant TLR- agonist Complement activation |
| url | https://hdl.handle.net/10171/20362 |
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