Murine and Non-Human Primate Dendritic Cell Targeting Nanoparticles for in Vivo Generation of Regulatory T-Cells

Sebastian O. Stead, Svjetlana Kireta, Steve J.P. McInnes, Francis D. Kette, Kisha N. Sivanathan, Juewan Kim, Eduardo J. Cueto-Diaz, Frederique Cunin, Jean Olivier Durand, Christopher J. Drogemuller, Robert P. Carroll, Nicolas H. Voelcker, Patrick T. Coates

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 + OVA 323-339 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.

Original languageEnglish
Pages (from-to)6637-6647
Number of pages11
JournalACS Nano
Volume12
Issue number7
DOIs
Publication statusPublished - 24 Jul 2018

Keywords

  • DC-SIGN
  • nanomedicine
  • nanoparticles
  • porous silicon
  • rapamycin
  • regulatory T-cells
  • tolerance

Cite this

Stead, S. O., Kireta, S., McInnes, S. J. P., Kette, F. D., Sivanathan, K. N., Kim, J., ... Coates, P. T. (2018). Murine and Non-Human Primate Dendritic Cell Targeting Nanoparticles for in Vivo Generation of Regulatory T-Cells. ACS Nano, 12(7), 6637-6647. https://doi.org/10.1021/acsnano.8b01625
Stead, Sebastian O. ; Kireta, Svjetlana ; McInnes, Steve J.P. ; Kette, Francis D. ; Sivanathan, Kisha N. ; Kim, Juewan ; Cueto-Diaz, Eduardo J. ; Cunin, Frederique ; Durand, Jean Olivier ; Drogemuller, Christopher J. ; Carroll, Robert P. ; Voelcker, Nicolas H. ; Coates, Patrick T. / Murine and Non-Human Primate Dendritic Cell Targeting Nanoparticles for in Vivo Generation of Regulatory T-Cells. In: ACS Nano. 2018 ; Vol. 12, No. 7. pp. 6637-6647.
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abstract = "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 + OVA 323-339 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.",
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Stead, SO, Kireta, S, McInnes, SJP, Kette, FD, Sivanathan, KN, Kim, J, Cueto-Diaz, EJ, Cunin, F, Durand, JO, Drogemuller, CJ, Carroll, RP, Voelcker, NH & Coates, PT 2018, 'Murine and Non-Human Primate Dendritic Cell Targeting Nanoparticles for in Vivo Generation of Regulatory T-Cells' ACS Nano, vol. 12, no. 7, pp. 6637-6647. https://doi.org/10.1021/acsnano.8b01625

Murine and Non-Human Primate Dendritic Cell Targeting Nanoparticles for in Vivo Generation of Regulatory T-Cells. / Stead, Sebastian O.; Kireta, Svjetlana; McInnes, Steve J.P.; Kette, Francis D.; Sivanathan, Kisha N.; Kim, Juewan; Cueto-Diaz, Eduardo J.; Cunin, Frederique; Durand, Jean Olivier; Drogemuller, Christopher J.; Carroll, Robert P.; Voelcker, Nicolas H.; Coates, Patrick T.

In: ACS Nano, Vol. 12, No. 7, 24.07.2018, p. 6637-6647.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Stead, Sebastian O.

AU - Kireta, Svjetlana

AU - McInnes, Steve J.P.

AU - Kette, Francis D.

AU - Sivanathan, Kisha N.

AU - Kim, Juewan

AU - Cueto-Diaz, Eduardo J.

AU - Cunin, Frederique

AU - Durand, Jean Olivier

AU - Drogemuller, Christopher J.

AU - Carroll, Robert P.

AU - Voelcker, Nicolas H.

AU - Coates, Patrick T.

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