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 journalArticle

14 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 - Feb 2018
Externally publishedYes

Keywords

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

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  • Cite this

    Stead, S. O., McInnes, S. J. P., Kireta, S., Rose, P. D., Jesudason, S., Rojas-Canales, D., Warther, D., Cunin, F., Durand, J. O., Drogemuller, C. J., Carroll, R. P., Coates, P. T., & Voelcker, N. H. (2018). Manipulating human dendritic cell phenotype and function with targeted porous silicon nanoparticles. Biomaterials, 155, 92-102. https://doi.org/10.1016/j.biomaterials.2017.11.017