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

Publication date: February 2018
Source:Biomaterials, Volume 155
Author(s): 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
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.



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