2. Academic Validation
  3. Elimination Pathways of Nanoparticles

Elimination Pathways of Nanoparticles

  • ACS Nano. 2019 May 28;13(5):5785-5798. doi: 10.1021/acsnano.9b01383.
Wilson Poon 1 2,  Yi-Nan Zhang 1 2,  Ben Ouyang 1 2 3,  Benjamin R Kingston 1 2,  Jamie L Y Wu 1 2,  Stefan Wilhelm 4 5,  Warren C W Chan 1 2 6 7 8
Affiliations

Affiliations

  • 1 Institute of Biomaterials and Biomedical Engineering , University of Toronto , Toronto , Ontario M5S 3G9 , Canada.
  • 2 Terrence Donnelly Centre for Cellular and Biomolecular Research , University of Toronto , Toronto , Ontario M5S 3E1 , Canada.
  • 3 MD/PhD Program, Faculty of Medicine , University of Toronto , Toronto , Ontario M5S 1A8 , Canada.
  • 4 Stephenson School of Biomedical Engineering , University of Oklahoma , Norman , Oklahoma 73019 , United States.
  • 5 Stephenson Cancer Center , Oklahoma City , Oklahoma 73104 , United States.
  • 6 Department of Chemical Engineering and Applied Chemistry , University of Toronto , Toronto , Ontario M5S 3E5 , Canada.
  • 7 Department of Materials Science and Engineering , University of Toronto , Toronto , Ontario M5S 1A1 , Canada.
  • 8 Department of Chemistry , University of Toronto , Toronto , Ontario M5S 3H6 , Canada.
PMID: 30990673 DOI: 10.1021/acsnano.9b01383
Abstract

Understanding how nanoparticles are eliminated from the body is required for their successful clinical translation. Many promising nanoparticle formulations for in vivo medical applications are large (>5.5 nm) and nonbiodegradable, so they cannot be eliminated renally. A proposed pathway for these nanoparticles is hepatobiliary elimination, but their transport has not been well-studied. Here, we explored the barriers that determined the elimination of nanoparticles through the hepatobiliary route. The route of hepatobiliary elimination is usually through the following pathway: (1) liver sinusoid, (2) space of Disse, (3) hepatocytes, (4) bile ducts, (5) intestines, and (6) out of the body. We discovered that the interaction of nanoparticles with liver nonparenchymal cells ( e. g., Kupffer cells and liver sinusoidal endothelial cells) determines the elimination fate. Each step in the route contains cells that can sequester and chemically or physically alter the nanoparticles, which influences their fecal elimination. We showed that the removal of Kupffer cells increased fecal elimination by >10 times. Combining our results with those of prior studies, we can start to build a systematic view of nanoparticle elimination pathways as it relates to particle size and Other design parameters. This is critical to engineering medically useful and translatable nanotechnologies.

Keywords

Kupffer cell; elimination; hepatobiliary; hepatocyte; liver; liver sinusoidal endothelial cell; nanoparticle.

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