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

doi:10.1016/j.biomaterials.2017.11.017

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

Biomaterials. 2018 Feb:155:92-102. doi: 10.1016/j.biomaterials.2017.11.017. Epub 2017 Nov 20.

Affiliations

¹ University of Adelaide, Department of Medicine, Adelaide, Australia.
² Future Industries Institute, University of South Australia, Adelaide, Australia.
³ Central Northern Adelaide Renal and Transplantation Service (CNARTS), The Royal Adelaide Hospital, Australia.
⁴ University of Adelaide, Department of Medicine, Adelaide, Australia; Central Northern Adelaide Renal and Transplantation Service (CNARTS), The Royal Adelaide Hospital, Australia.
⁵ Institut Charles Gerhardt Montpellier, UMR 5253 CNRS -ENSCM-UM2-UM1, Ecole Nationale Supérieure de Chimie de Montpellier, 34296, Montpellier, France.
⁶ University of Adelaide, Department of Medicine, Adelaide, Australia; Central Northern Adelaide Renal and Transplantation Service (CNARTS), The Royal Adelaide Hospital, Australia. Electronic address: toby.coates@sa.gov.au.
⁷ Future Industries Institute, University of South Australia, Adelaide, Australia; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria, Australia; Commonwealth Scientific and Industrial Research Organisation (CSIRO), Clayton, VIC, Australia; Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, Clayton, VIC, Australia; Monash Institute of Medical Engineering, Monash University, Clayton, Victoria, Australia. Electronic address: nicolas.voelcker@monash.edu.

PMID: 29175084
DOI: 10.1016/j.biomaterials.2017.11.017

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.

Keywords: Dendritic cells; Immunomodulation; Nanomedicine; Nanoparticles; Porous silicon; Rapamycin; Targeting.

MeSH terms

Dendritic Cells / drug effects*
Dendritic Cells / immunology
Humans
Nanomedicine
Nanoparticles / chemistry*
Porosity
Silicon / chemistry*

Substances

Silicon