The effect of neutral-surface iron oxide nanoparticles on cellular uptake and signaling pathways

Int J Nanomedicine. 2016 Sep 13:11:4595-4607. doi: 10.2147/IJN.S110332. eCollection 2016.

Abstract

In recent years, iron oxide nanoparticles (IONPs) have been applied widely to biomedical fields. However, the relationship between the physicochemical properties of IONPs and their biological behavior is not fully understood yet. We prepared 3-methacryloxypropyltrimethoxysilane (MPS)-coated IONPs, which have a neutral hydrophobic surface, and compared their biological behavior to that of Resovist (ferucarbotran), a commercialized IONP formulation modified with carboxymethyl dextran. The rate of MPS-IONP uptake by human aortic endothelial cells (HAoECs) was higher than ferucarbotran uptake, indicating that the neutral hydrophobic nature of MPS-IONPs allowed them to be absorbed more readily through the plasma membrane. However, the signaling pathways activated by MPS-IONPs and ferucarbotran were comparable, suggesting that surface charge is not a key factor for inducing changes in HAoECs. In vivo fate analysis showed that MPS-IONPs accumulated for longer periods in tissues than hydrophilic ferucarbotran. These findings could enlarge our understanding of NP behavior for advanced applications in the biomedical field.

Keywords: accumulation; iron oxide nanoparticles; neutral hydrophobic surface; reactive oxygen species (ROS); signaling pathway; uptake.

MeSH terms

  • Animals
  • Cell Death
  • Cell Line
  • Dextrans / chemistry
  • Endocytosis*
  • Endothelial Cells / metabolism
  • Ferric Compounds / chemistry*
  • Gene Expression Profiling
  • Humans
  • Iron / metabolism
  • Magnetite Nanoparticles / chemistry
  • Methacrylates / chemistry
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Signal Transduction*
  • Silanes / chemistry
  • Spectroscopy, Fourier Transform Infrared
  • Tissue Distribution

Substances

  • 3-methacryloxypropyltrimethoxysilane
  • Dextrans
  • Ferric Compounds
  • Magnetite Nanoparticles
  • Methacrylates
  • Reactive Oxygen Species
  • Silanes
  • ferric oxide
  • Iron
  • ferumoxides