Please use this identifier to cite or link to this item: https://doi.org/10.3390/ijms20010035
Title: Titanium dioxide nanoparticles enhance leakiness and drug permeability in primary human hepatic sinusoidal endothelial cells
Authors: Tee, J.K 
Ng, L.Y
Koh, H.Y
Leong, D.T 
Ho, H.K 
Keywords: nanoparticle
titanium dioxide
protein kinase B
titanium
titanium dioxide
apoptosis
Article
cell adhesion
cell proliferation
cell viability
chronic liver disease
disease exacerbation
drug delivery system
drug penetration
endothelium cell
enzyme linked immunosorbent assay
flow cytometry
human
human cell
immunofluorescence
liver cell
liver sinusoidal endothelial cell
oxidative stress
particle size
protein expression
real time polymerase chain reaction
signal transduction
Western blotting
zeta potential
cell communication
cell culture
cell survival
chemistry
cytology
drug effect
endothelium cell
liver
liver cell
metabolism
pathology
permeability
Cell Communication
Cell Survival
Cells, Cultured
Endothelial Cells
Hepatocytes
Humans
Liver
Nanoparticles
Oxidative Stress
Permeability
Proto-Oncogene Proteins c-akt
Signal Transduction
Titanium
Issue Date: 2019
Citation: Tee, J.K, Ng, L.Y, Koh, H.Y, Leong, D.T, Ho, H.K (2019). Titanium dioxide nanoparticles enhance leakiness and drug permeability in primary human hepatic sinusoidal endothelial cells. International Journal of Molecular Sciences 20 (1) : 35. ScholarBank@NUS Repository. https://doi.org/10.3390/ijms20010035
Abstract: Liver sinusoidal endothelial cells (LSECs) represent the permeable interface that segregates the blood compartment from the hepatic cells, regulating hepatic vascular tone and portal pressure amidst changes in the blood flow. In the presence of pathological conditions, phenotypic changes in LSECs contribute to the progression of chronic liver diseases, including the loss of endothelial permeability. Therefore, modulating LSECs offers a possible way to restore sinusoidal permeability and thereby improve hepatic recovery. Herein, we showed that titanium dioxide nanoparticles (TiO 2 NPs) could induce transient leakiness in primary human hepatic sinusoidal endothelial cells (HHSECs). Interestingly, HHSECs exposed to these NPs exhibited reduced protein kinase B (Akt) phosphorylation, an important protein kinase which regulates cell attachment. Using a 3D co-culture system, we demonstrated that TiO 2 NPs diminished the attachment of HHSECs onto normal human hepatic cell LO2. To further illustrate the significance of leakiness in liver sinusoids, we showed that NP-induced leakiness promoted Sunitinib transport across the HHSEC layer, resulting in increased drug uptake and efficacy. Hence, TiO 2 NPs have the potential to modulate endothelial permeability within the specialized sinusoidal endothelium, especially during events of fibrosis and occlusion. This study highlighted the possible use of inorganic NPs as a novel strategy to promote drug delivery targeting the diseased liver. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Source Title: International Journal of Molecular Sciences
URI: https://scholarbank.nus.edu.sg/handle/10635/176190
ISSN: 1661-6596
DOI: 10.3390/ijms20010035
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