Demonstrating approaches to chemically modify the surface of Ag nanoparticles in order to influence their cytotoxicity and biodistribution after single dose acute intravenous administration

Nanotoxicology. 2016;10(2):129-39. doi: 10.3109/17435390.2015.1024295. Epub 2015 May 12.


With the advance in material science and the need to diversify market applications, silver nanoparticles (AgNPs) are modified by different surface coatings. However, how these surface modifications influence the effects of AgNPs on human health is still largely unknown. We have evaluated the uptake, toxicity and pharmacokinetics of AgNPs coated with citrate, polyethylene glycol, polyvinyl pyrolidone and branched polyethyleneimine (Citrate AgNPs, PEG AgNPs, PVP AgNPs and BPEI AgNPs, respectively). Our results demonstrated that the toxicity of AgNPs depends on the intracellular localization that was highly dependent on the surface charge. BPEI AgNPs (ζ potential = +46.5 mV) induced the highest cytotoxicity and DNA fragmentation in Hepa1c1c7. In addition, it showed the highest damage to the nucleus of liver cells in the exposed mice, which is associated with a high accumulation in liver tissues. The PEG AgNPs (ζ potential = -16.2 mV) showed the cytotoxicity, a long blood circulation, as well as bioaccumulation in spleen (34.33 µg/g), which suggest better biocompatibility compared to the other chemically modified AgNPs. Moreover, the adsorption ability with bovine serum albumin revealed that the PEG surface of AgNPs has an optimal biological inertia and can effectively resist opsonization or non-specific binding to protein in mice. The overall results indicated that the biodistribution of AgNPs was significantly dependent on surface chemistry: BPEI AgNPs > Citrate AgNPs = PVP AgNPs > PEG AgNPs. This toxicological data could be useful in supporting the development of safe AgNPs for consumer products and drug delivery applications.

Keywords: Acute toxicity; pharmacokinetics; protein sorption; surface coating.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous*
  • Adsorption
  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chemistry, Pharmaceutical
  • Citric Acid / chemistry
  • DNA Fragmentation / drug effects
  • Male
  • Metal Nanoparticles / administration & dosage
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / toxicity*
  • Mice
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Polyethyleneimine / chemistry
  • Povidone / analogs & derivatives
  • Povidone / chemistry
  • Serum Albumin, Bovine / chemistry
  • Silver / administration & dosage
  • Silver / blood
  • Silver / pharmacokinetics*
  • Silver / toxicity*
  • Surface Properties
  • Tissue Distribution


  • polyvinylpolypyrrolidone
  • Serum Albumin, Bovine
  • Citric Acid
  • Silver
  • Polyethylene Glycols
  • Polyethyleneimine
  • Povidone