Influence of silver and titanium dioxide nanoparticles on in vitro blood-brain barrier permeability.
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; 8nm) and TiO2nanoparticles (TiO2NPs; 6nm and 35nm) 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.
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu, 30013, Taiwan. Electronic address: ejchen00@gmail.com.
I-Chieh
IC
Chen
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu, 30013, Taiwan. Electronic address: ilunshiou@gmail.com.
I-Lun
IL
Hsiao
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu, 30013, Taiwan. Electronic address: photorice2@gmail.com.
Ho-Chen
HC
Lin
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu, 30013, Taiwan. Electronic address: chwu@mx.nthu.edu.tw.
Chien-Hou
CH
Wu
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu, 30013, Taiwan. Electronic address: cychuang@mx.nthu.edu.tw.
Chun-Yu
CY
Chuang
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu, 30013, Taiwan. Electronic address: yjhuang@mx.nthu.edu.tw.
Yuh-Jeen
YJ
Huang
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D062507:Claudin-5 / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010539:Permeability; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000493:pharmacokinetics / Q000633:toxicity*; D014025:Titanium / Q000493:pharmacokinetics / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
D062507:Claudin-5; C491511:Cldn5 protein, mouse; D016207:Cytokines; D017382:Reactive Oxygen Species; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; C009495:titanium dioxide; D012834:Silver; D014025:Titanium
In vitro blood-brain barrier; Permeability; Silver ions; Silver nanoparticles; Titanium dioxide nanoparticles