Journal
BIOMATERIALS
Volume 43, Issue -, Pages 1-12Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.11.045
Keywords
Gold nanoclusters; Fluorescence; Cellular uptake; Immune response; Monocyte-derived dendritic cells
Funding
- Institut de Salud Carlos III (ISCII) [CP12/03310]
- European Regional Development Fund (ERDF)
- FIS-Thematic Networks and Co-operative Research Centres: RIRAAF [RD012/0013]
- Junta de Andalucia [CTS-7433]
- ISCIII [P112/02481-PI/02529]
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We have studied the effect of highly fluorescent gold nanoclusters (Au NCs) (0 < 3 nm) stabilized by different ligands on the intracellular accumulation and immune response of human derived-monocyte dendritic cells (DCs). Results indicate that the high uptake efficiency of Au NCs is strongly related to their small size and to the nature of the ligand, with zwitterionic ligands being more effective than PEGylated ones. Evidence from flow cytometry and microscopy demonstrate time and concentration-dependent Au NCs internalization by endocytic pathway(s) involving amorphous and laminar organelles, while maintaining their discrete size and photoluminescence properties. The uptake of zwitterionic ligand-stabilized Au NCs induced very low cytotoxicity and a strong immunosuppressive response (Thu/ Treg pattern), associated with a DC maturation state. This behavior contrasts to the effect of bigger particles (similar to 12 nm size) which induced a cytotoxic response involving Natural Killer (CD56) cells. Overall, this study stresses the critical importance of particle size and ligand type on the immunostimulation of DCs and highlights the remarkable potential of this new class of nanomaterial as a novel vaccine platform. (C) 2014 Elsevier Ltd. All rights reserved.
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