Biodistribution of TNF-alpha-coated gold nanoparticles in an in vivo model system

Nanomedicine (Lond). 2009 Jun;4(4):401-10. doi: 10.2217/nnm.09.21.

Abstract

Aim: In this study, we describe the biodistribution of CYT-6091, a colloidal gold (Au)-based nanomedicine that targets the delivery of TNF-alpha to solid tumors.

Materials & methods: A single intravenous injection of CYT-6091 coated with 5 microg TNF-alpha was given to human prostate tumor-bearing or naive (without tumor) nude mice. Tissues were harvested and analyzed at specific time points for Au nanoparticles by atomic emission spectroscopy and TNF-alpha by ELISA.

Results: The two constituents of CYT-6091, TNF-alpha and Au, exhibited different behavior in blood, with TNF-alpha showing a faster decay than the Au nanoparticles. Between 0 and 4 h after injection, TNF-alpha showed a preferential accumulation in the tumor. Au was observed to accumulate preferentially in the liver between 4 and 12 h, and showed some clearance over time (4 months).

Conclusion: These data suggest that CYT-6091 delivers TNF-alpha preferentially to the tumor and that upon TNF-alpha degradation, the liver takes up Au, which is cleared slowly over time.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gold Colloid / chemistry*
  • Humans
  • Liver / metabolism
  • Liver / ultrastructure
  • Male
  • Mice
  • Mice, Nude
  • Microscopy, Electron, Transmission
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / ultrastructure
  • Spleen / metabolism
  • Spleen / ultrastructure
  • Tumor Necrosis Factor-alpha / chemistry*
  • Tumor Necrosis Factor-alpha / pharmacokinetics*
  • Tumor Necrosis Factor-alpha / therapeutic use

Substances

  • Gold Colloid
  • Tumor Necrosis Factor-alpha