Influence of silver and titanium dioxide nanoparticles on in vitro blood-brain barrier permeability

I. Chieh Chen, I. Lun Hsiao, Ho Chen Lin, Chien Hou Wu, Chun Yu Chuang, Yuh Jeen Huang

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)


An in vitro blood-brain barrier (BBB) model being composed of co-culture with endothelial (bEnd.3) and astrocyte-like (ALT) cells was established to evaluate the toxicity and permeability of Ag nanoparticles (AgNPs; 8 nm) and TiO2 nanoparticles (TiO2NPs; 6 nm and 35 nm) in normal and inflammatory central nervous system. Lipopolysaccharide (LPS) was pre-treated to simulate the inflammatory responses. Both AgNPs and Ag ions can decrease transendothelial electrical resistance (TEER) value, and cause discontinuous tight junction proteins (claudin-5 and zonula occludens-1) of BBB. However, only the Ag ions induced inflammatory cytokines to release, and had less cell-to-cell permeability than AgNPs, which indicated that the toxicity of AgNPs was distinct from Ag ions. LPS itself disrupted BBB, while co-treatment with AgNPs and LPS dramatically enhanced the disruption and permeability coefficient. On the other hand, TiO2NPs exposure increased BBB penetration by size, and disrupted tight junction proteins without size dependence, and many of TiO2NPs accumulated in the endothelial cells were observed. This study provided the new insight of toxic potency of AgNPs and TiO2NPs in BBB.

Original languageEnglish
Pages (from-to)108-118
Number of pages11
JournalEnvironmental Toxicology and Pharmacology
Publication statusPublished - Oct 1 2016
Externally publishedYes


  • In vitro blood-brain barrier
  • Permeability
  • Silver ions
  • Silver nanoparticles
  • Titanium dioxide nanoparticles

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis


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