Biological safety and tissue distribution of (16-mercaptohexadecyl)trimethylammonium bromide-modified cationic gold nanorods

Biomaterials. 2018 Feb:154:275-290. doi: 10.1016/j.biomaterials.2017.10.044. Epub 2017 Nov 1.

Abstract

The exceptionally high cellular uptake of gold nanorods (GNRs) bearing cationic surfactants makes them a promising tool for biomedical applications. Given the known specific toxic and stress effects of some preparations of cationic nanoparticles, the purpose of this study was to evaluate, in an in vitro and in vivo in mouse, the potential harmful effects of GNRs coated with (16-mercaptohexadecyl)trimethylammonium bromide (MTABGNRs). Interestingly, even after cellular accumulation of high amounts of MTABGNRs sufficient for induction of photothermal effect, no genotoxicity (even after longer-term accumulation), induction of autophagy, destabilization of lysosomes (dominant organelles of their cellular destination), alterations of actin cytoskeleton, or in cell migration could be detected in vitro. In vivo, after intravenous administration, the majority of GNRs accumulated in mouse spleen followed by lungs and liver. Microscopic examination of the blood and spleen showed that GNRs interacted with white blood cells (mononuclear and polymorphonuclear leukocytes) and thrombocytes, and were delivered to the spleen red pulp mainly as GNR-thrombocyte complexes. Importantly, no acute toxic effects of MTABGNRs administered as 10 or 50 μg of gold per mice, as well as no pathological changes after their high accumulation in the spleen were observed, indicating good tolerance of MTABGNRs by living systems.

Keywords: Autophagy; Genotoxicity; Lysosomal stress; Plasmonic photothermal effect; Spleen; Thrombocytes.

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / metabolism
  • Animals
  • Autophagy / drug effects
  • Blood Platelets / drug effects
  • Blood Platelets / pathology
  • Blood Platelets / ultrastructure
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • DNA Damage
  • Gold / metabolism*
  • Humans
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mice, Inbred C57BL
  • Mutagens / toxicity
  • Nanotubes / chemistry*
  • Nanotubes / toxicity
  • Nanotubes / ultrastructure
  • Podocytes / drug effects
  • Podocytes / metabolism
  • Quaternary Ammonium Compounds / metabolism*
  • Spleen / drug effects
  • Spleen / pathology
  • Sulfhydryl Compounds / metabolism*
  • Tissue Distribution

Substances

  • (16-mercaptohexadecyl)trimethylammonium bromide
  • Mutagens
  • Quaternary Ammonium Compounds
  • Sulfhydryl Compounds
  • Gold