Manipulating human dendritic cell phenotype and function with targeted porous silicon nanoparticles

Sebastian O. Stead, Steven J.P. McInnes, Svjetlana Kireta, Peter D. Rose, Shilpanjali Jesudason, Darling Rojas-Canales, David Warther, Frédérique Cunin, Jean Olivier Durand, Christopher J. Drogemuller, Robert P. Carroll, P. Toby Coates, Nicolas H. Voelcker

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

Dendritic cells (DC) are the most potent antigen-presenting cells and are fundamental for the establishment of transplant tolerance. The Dendritic Cell-Specific Intracellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN; CD209) receptor provides a target for dendritic cell therapy. Biodegradable and high-surface area porous silicon (pSi) nanoparticles displaying anti-DC-SIGN antibodies and loaded with the immunosuppressant rapamycin (Sirolimus) serve as a fit-for-purpose platform to target and modify DC. Here, we describe the fabrication of rapamycin-loaded DC-SIGN displaying pSi nanoparticles, the uptake efficiency into DC and the extent of nanoparticle-induced modulation of phenotype and function. DC-SIGN antibody displaying pSi nanoparticles favourably targeted and were phagocytosed by monocyte-derived and myeloid DC in whole human blood in a time- and dose-dependent manner. DC preconditioning with rapamycin-loaded nanoparticles, resulted in a maturation resistant phenotype and significantly suppressed allogeneic T-cell proliferation.

Original languageEnglish
Pages (from-to)92-102
Number of pages11
JournalBiomaterials
Volume155
DOIs
Publication statusPublished - 1 Feb 2018

Keywords

  • Dendritic cells
  • Immunomodulation
  • Nanomedicine
  • Nanoparticles
  • Porous silicon
  • Rapamycin
  • Targeting

Cite this

Stead, Sebastian O. ; McInnes, Steven J.P. ; Kireta, Svjetlana ; Rose, Peter D. ; Jesudason, Shilpanjali ; Rojas-Canales, Darling ; Warther, David ; Cunin, Frédérique ; Durand, Jean Olivier ; Drogemuller, Christopher J. ; Carroll, Robert P. ; Coates, P. Toby ; Voelcker, Nicolas H. / Manipulating human dendritic cell phenotype and function with targeted porous silicon nanoparticles. In: Biomaterials. 2018 ; Vol. 155. pp. 92-102.
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author = "Stead, {Sebastian O.} and McInnes, {Steven J.P.} and Svjetlana Kireta and Rose, {Peter D.} and Shilpanjali Jesudason and Darling Rojas-Canales and David Warther and Fr{\'e}d{\'e}rique Cunin and Durand, {Jean Olivier} and Drogemuller, {Christopher J.} and Carroll, {Robert P.} and Coates, {P. Toby} and Voelcker, {Nicolas H.}",
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Stead, SO, McInnes, SJP, Kireta, S, Rose, PD, Jesudason, S, Rojas-Canales, D, Warther, D, Cunin, F, Durand, JO, Drogemuller, CJ, Carroll, RP, Coates, PT & Voelcker, NH 2018, 'Manipulating human dendritic cell phenotype and function with targeted porous silicon nanoparticles', Biomaterials, vol. 155, pp. 92-102. https://doi.org/10.1016/j.biomaterials.2017.11.017

Manipulating human dendritic cell phenotype and function with targeted porous silicon nanoparticles. / Stead, Sebastian O.; McInnes, Steven J.P.; Kireta, Svjetlana; Rose, Peter D.; Jesudason, Shilpanjali; Rojas-Canales, Darling; Warther, David; Cunin, Frédérique; Durand, Jean Olivier; Drogemuller, Christopher J.; Carroll, Robert P.; Coates, P. Toby; Voelcker, Nicolas H.

In: Biomaterials, Vol. 155, 01.02.2018, p. 92-102.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

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AU - Stead, Sebastian O.

AU - McInnes, Steven J.P.

AU - Kireta, Svjetlana

AU - Rose, Peter D.

AU - Jesudason, Shilpanjali

AU - Rojas-Canales, Darling

AU - Warther, David

AU - Cunin, Frédérique

AU - Durand, Jean Olivier

AU - Drogemuller, Christopher J.

AU - Carroll, Robert P.

AU - Coates, P. Toby

AU - Voelcker, Nicolas H.

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AB - Dendritic cells (DC) are the most potent antigen-presenting cells and are fundamental for the establishment of transplant tolerance. The Dendritic Cell-Specific Intracellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN; CD209) receptor provides a target for dendritic cell therapy. Biodegradable and high-surface area porous silicon (pSi) nanoparticles displaying anti-DC-SIGN antibodies and loaded with the immunosuppressant rapamycin (Sirolimus) serve as a fit-for-purpose platform to target and modify DC. Here, we describe the fabrication of rapamycin-loaded DC-SIGN displaying pSi nanoparticles, the uptake efficiency into DC and the extent of nanoparticle-induced modulation of phenotype and function. DC-SIGN antibody displaying pSi nanoparticles favourably targeted and were phagocytosed by monocyte-derived and myeloid DC in whole human blood in a time- and dose-dependent manner. DC preconditioning with rapamycin-loaded nanoparticles, resulted in a maturation resistant phenotype and significantly suppressed allogeneic T-cell proliferation.

KW - Dendritic cells

KW - Immunomodulation

KW - Nanomedicine

KW - Nanoparticles

KW - Porous silicon

KW - Rapamycin

KW - Targeting

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M3 - Article

C2 - 29175084

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VL - 155

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EP - 102

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

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