Investigating the localization and anti-inflammatory effects of gold nanoparticles in the central nervous system of mice

Details

• Personal Author:
  Fallahi F ; Hussain SM ; O'Callaghan JP ; Pavel Sizemore IE
• Description:
  Unique physicochemical properties of gold nanoparticles (GNPs) makes them a good candidate for drug delivery and targeted treatment of CNS diseases. However, if we want to utilize GNPs for the treatment of CNS disorders, it is crucial to verify that GNPs pass the BBB and reach the neuronal tissue of brain. Brain localization and neuroinflammatory response to citrate-capped spherical GNP (10 nm) was determined 24 hours after IV injection in male C57Bl/6 mice. Initial testing of various concentrations of PBS determined that 0.01 X PBS produced the least amount of aggregation while maintaining GNP solubility. In the next step, mice were injected IV (200 microg/mL 10 nm GNP in 0.01 X PBS) via the tail vein. 24 hours after IV injection mice were perfused transcardially with 2% glutaraldehyde and 2% paraformaldehyde, then brains were collected. Inductively coupled plasma mass spectrometry was utilized to measure the GNPs concentrations of the whole brain and to further quantify concentration of GNPs in specific brain regions. Dissection of septum, caudate, hippocampus, hypothalamus, cortex, frontal cortex, and spinal cord indicated that hypothalamus, hippocampus, and septum had the highest level of GNPs. q-PCR analysis of above metioned brain regions was used to measure the level of pro-inflammatory mediators such as; LIF, CCL2 and IL-1alpha and the brain inflammation. Results revealed no significant increase of proinflammatory cytokine/chemokine expressions. However, significant downregulation of IL-1alpha expression in frontal cortex may indicate that IL-1alpha molecules were accumulated near the surface of GNPs, which reduced their interaction with interleukin receptors. Finally, it was concluded that GNPs enter brain and accumulated in specific regions without stimulating an inflammatory response. Results verified that GNPs can effectively be used in targeted drug delivery and therapeutic treatment of CNS diseases. [Description provided by NIOSH]
• Subjects:
  Animals Biopharmaceutics Laboratories Nervous System Nervous System Disorders Occupational Health Safety Toxicology
• Keywords:
  Animal-studies Central-nervous-system-disorders Laboratory-animals Nanotechnology Pharmaceuticals Treatment
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; Ohio ; OSHA Region 3 ; OSHA Region 5 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20045999
• Citation:
  Toxicologist 2015 Mar; 144(1):507
• CAS Registry Number:
  Gold (CAS RN 7440-57-5)
• Federal Fiscal Year:
  2015
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f4a6bb969a266097ba8c1a15f52cdff23be171e21825f4007839905cfc5894af039fdd83b1f58856121af8906a8d28d3e59869f184fda35d28161cce15970071
• Download URL:
  https://stacks.cdc.gov/view/cdc/201197/cdc_201197_DS1.pdf
• File Type:
  [PDF - 219.52 KB ]