Intracellular accumulation and immunological properties of fluorescent gold nanoclusters in human dendritic cells

Biomaterials. 2015 Mar;43:1-12. doi: 10.1016/j.biomaterials.2014.11.045. Epub 2014 Dec 18.

Abstract

We have studied the effect of highly fluorescent gold nanoclusters (Au NCs) (∅ < 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 (Th1/Treg pattern), associated with a DC maturation state. This behavior contrasts to the effect of bigger particles (∼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.

Keywords: Cellular uptake; Fluorescence; Gold nanoclusters; Immune response; Monocyte-derived dendritic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • CD56 Antigen / metabolism
  • Cell Proliferation
  • Dendritic Cells / drug effects*
  • Dose-Response Relationship, Drug
  • Endocytosis
  • Flow Cytometry
  • Fluorescent Dyes / chemistry*
  • Gold / chemistry*
  • Humans
  • Immune System
  • Immunosuppressive Agents / chemistry
  • Ligands
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Metal Nanoparticles / chemistry*
  • Microscopy, Confocal
  • Nanomedicine
  • Particle Size

Substances

  • Amines
  • CD56 Antigen
  • Fluorescent Dyes
  • Immunosuppressive Agents
  • Ligands
  • Gold