Tissue biodistribution of intravenously administrated titanium dioxide nanoparticles revealed blood-brain barrier clearance and brain inflammation in rat

Particle and Fibre Toxicology
Clémence DisdierAloïse Mabondzo

Abstract

Notwithstanding increasing knowledge of titanium dioxide nanoparticles (TiO2 NPs) passing through biological barriers, their biodistribution to the central nervous system (CNS) and potential effects on blood-brain barrier (BBB) physiology remain poorly characterized. Here, we report time-related responses from single-dose intravenous (IV) administration of 1 mg/kg TiO2 NPs to rats, with particular emphasis on titanium (Ti) quantification in the brain. Ti content in tissues was analyzed using inductively coupled plasma mass spectrometry. Integrity and functionality of the BBB as well as brain inflammation were characterized using a panel of methods including RT-PCR, immuno-histo chemistry and transporter activity evaluation. Biokinetic analysis revealed Ti biopersistence in liver, lungs and spleen up to one year after TiO2 NPs administration. A significant increase of Ti in the brain was observed at early end points followed by a subsequent decrease. In-depth analysis of Ti in the total brain demonstrated quantitative Ti uptake and clearance by brain microvasculature endothelial cells (BECs) with minimal translocation in the brain parenchyma. The presence of Ti in the BECs did not affect BBB integrity, despite rapid reversible m...Continue Reading

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Methods Mentioned

BETA
X-ray
PCR
Scanning
Dynamic Light Scattering
profiler
fluorescence microscopy

Software Mentioned

LC Quan
SigmaPlot SyStat
GraphPad
Match
Prism
Image J
Xcalibur

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