Murine and Non-Human Primate Dendritic Cell Targeting Nanoparticles for in Vivo Generation of Regulatory T-Cells
| Autor: | Robert P. Carroll, Patrick T. Coates, Juewan Kim, Chris Drogemuller, Nicolas H. Voelcker, Francis D. Kette, Jean-Olivier Durand, Sebastian O. Stead, Frédérique Cunin, Steven J. P. McInnes, Kisha N. Sivanathan, Eduardo J. Cueto-Díaz, Svjetlana Kireta |
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| Přispěvatelé: | Stead, Sebastian O, Kireta, Svjetlana, McInnes, Steve JP, Kette, Francis D, Sivanathan, Kisha N, Kim, Juewan, Cueto-Diaz, Eduardo J, Cunin, Frederique, Durand, Jean Olivier, Drogemuller, Christopher J, Carroll, Robert P, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Mawson Institute, University of South Australia |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Immunoconjugates General Physics and Astronomy 02 engineering and technology T-Lymphocytes Regulatory Drug Delivery Systems General Materials Science tolerance biology medicine.diagnostic_test Chemistry General Engineering Antibodies Monoclonal FOXP3 Callithrix 021001 nanoscience & nanotechnology nanomedicine 3. Good health Cell biology DC-SIGN porous silicon medicine.anatomical_structure 0210 nano-technology Immunosuppressive Agents Silicon Ovalbumin medicine.drug_class CD11c Receptors Cell Surface Spleen Monoclonal antibody Flow cytometry 03 medical and health sciences In vivo medicine [CHIM]Chemical Sciences Animals Lectins C-Type Sirolimus rapamycin Dendritic Cells Dendritic cell regulatory T-cells CD11c Antigen Mice Inbred C57BL 030104 developmental biology biology.protein Nanoparticles Cell Adhesion Molecules |
| Zdroj: | ACS Nano ACS Nano, American Chemical Society, 2018, 12 (7), pp.6637-6647. ⟨10.1021/acsnano.8b01625⟩ |
| ISSN: | 1936-086X 1936-0851 |
| DOI: | 10.1021/acsnano.8b01625 |
| Popis: | International audience; Porous silicon nanoparticles (pSiNP), modified to target dendritic cells (DC), provide an alternate strategy for the delivery of immunosuppressive drugs. Here, we aimed to develop a DC-targeting pSiNP displaying c-type lectin, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), and CD11c monoclonal antibodies. The in vivo tracking of these fluorescent DC-targeting nanoparticles was assessed in both C57BL/6 mice and common marmosets (Callithrix jacchus) by intravenous injection (20 mg/kg). Rapamycin and ovalbumin (OVA)323–339 peptide loaded pSiNP were employed to evaluate their ability to generate murine CD4+CD25+FoxP3+ regulatory T-cells in vivo within OVA sensitized mice. In vivo, pSiNP migrated to the liver, kidneys, lungs, and spleen in both mice and marmosets. Flow cytometry confirmed pSiNP uptake by splenic and peripheral blood DC when functionalized with targeting antibodies. C57BL/6 OVA sensitized mice injected with CD11c-pSiNP loaded with rapamycin + OVA323–339 produced a 5-fold higher number of splenic regulatory T-cells compared to control mice, at 40 days post-pSiNP injection. These results demonstrate the importance of the immobilized targeting antibodies to enhance cellular uptake and enable the in vivo generation of splenic regulatory T-cells. |
| Databáze: | OpenAIRE |
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