Cellular Uptake and Tissue Biodistribution of Functionalized Gold Nanoparticles and Nanoclusters

J Biomed Nanotechnol. 2017 Feb;13(2):167-79.

Abstract

In this study, the in vitro uptake by fibroblasts and in vivo biodistribution of 15 nm 11-mercaptoundecanoicacid-protected gold nanoparticles (AuNPs-MUA) and 3 nm glutathione- and 3 nm bovine serum albumin-protected gold nanoclusters (AuNCs@GSH and AuNCs@BSA, respectively) were evaluated. In vitro cell viability was examined after gold nanoparticle treatment for 48 h, based on MTT assays and analyses of morphological structure, the cycle cell, cellular doubling time, and the gold concentration in cells. No potential toxicity was observed at any studied concentration (up to 10 ppm) for AuNCs@GSH and AuNCs@BSA, whereas lower cell viability was observed for AuNPs-MUA at 10 ppm than for other treatments. Neither morphological damage nor modifications to the cell cycle and doubling time were detected after contact with nanoparticles. Associations between cells and AuNPs and AuNCs were demonstrated by inductively coupled plasma mass spectrometry (ICP-MS). AuNCs@GSH exhibited fluorescence emission at 611 nm, whereas AuNCs@BSA showed a band at 640 nm. These properties were employed to confirm their associations with cells by fluorescence confocal microscopy; both clusters were observed in cells and maintained their original fluorescence. In vivo assays were performed using 9 male mice treated with 1.70 μg Au/g body weight gold nanoparticles for 24 h. ICP-MS measurements showed a different biodistribution for each type of nanoparticle; AuNPs-MUA mainly accumulated in the brain, AuNCs@GSH in the kidney, and AuNCs@BSA in the liver and spleen. Spleen indexes were not affected by nanoparticle treatment; however, AuNCs@BSA increased the thymus index significantly from 1.28 to 1.79, indicating an immune response. These nanoparticles have great potential as organ-specific drug carriers and for diagnosis, photothermal therapy, and imaging.

Keywords: Gold nanoparticles; Toxicity; Cellular Uptake; Biodistribution; Nanotechnology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Glutathione
  • Gold / chemistry*
  • Gold / pharmacokinetics*
  • Gold / toxicity
  • Liver / chemistry
  • Liver / metabolism
  • Male
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / toxicity
  • Mice
  • Mice, Inbred C57BL
  • NIH 3T3 Cells
  • Serum Albumin, Bovine
  • Spleen / chemistry
  • Spleen / metabolism
  • Tissue Distribution

Substances

  • Serum Albumin, Bovine
  • Gold
  • Glutathione