Citrate-stabilized lanthanide-doped nanoparticles: brain penetration and interaction with immune cells and neurons

Nanomedicine (Lond). 2016 Dec;11(23):3039-3051. doi: 10.2217/nnm-2016-0297. Epub 2016 Nov 4.

Abstract

Aim: To unravel key aspects of the use of lanthanide-doped nanoparticles (NPs) in biomedicine, the interaction with immune and brain cells.

Materials & methods: Effects of citrate-stabilized CaF2 and SrF2: Yb, Er NPs (13-15 nm) on human dendritic cells and neurons were assessed in vitro. In vivo distribution was analyzed in mice at tissue and ultrastructural levels, and with glia immunophenotyping.

Results: The NPs did not elicit dendritic cell activation and were internalized by cultured neurons, without viability changes. After intravenous injection, NPs were found in the brain parenchyma, without features of glial neuroinflammatory response.

Conclusion: Lanthanide-doped NPs do not activate cells protagonists of systemic and brain immune responses, are endocytosed by neurons and can cross an intact blood-brain barrier.

Keywords: biodistribution; bioimaging; blood–brain barrier; cytokines; dendritic cells; endocytosis; glia; immune response; lanthanide-doped nanoparticles.

MeSH terms

  • Animals
  • Biological Transport
  • Blood-Brain Barrier / metabolism
  • Brain / diagnostic imaging*
  • Brain / immunology
  • Calcium Fluoride / chemistry
  • Cell Survival
  • Cells, Cultured
  • Citric Acid / chemistry*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Endocytosis
  • Europium / chemistry
  • Humans
  • Lanthanoid Series Elements / chemistry*
  • Male
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Neuroglia / immunology
  • Neuroglia / metabolism
  • Neurons / metabolism*
  • Optical Imaging
  • Particle Size
  • Permeability
  • Strontium / chemistry
  • Tissue Distribution
  • Ytterbium / chemistry

Substances

  • Lanthanoid Series Elements
  • Citric Acid
  • Europium
  • Ytterbium
  • Calcium Fluoride
  • Strontium