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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
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Polystyrene nanoparticle trafficking across MDCK-II.

Farnoosh Fazlollahi1, Susanne Angelow, Nazanin R Yacobi

  • 1Will Rogers Institute Pulmonary Research Center, University of Southern California, Los Angeles, California 90033, USA. fazlolla@usc.edu

Nanomedicine : Nanotechnology, Biology, and Medicine
|February 12, 2011
PubMed
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Polystyrene nanoparticles (PNP) cross kidney cell monolayers via clathrin-mediated endocytosis, not non-endocytic pathways. Nanoparticle properties and cell type significantly influence this transport.

Area of Science:

  • Nanomedicine
  • Cell Biology
  • Toxicology

Background:

  • Polystyrene nanoparticles (PNP) are known to cross epithelial barriers.
  • The mechanisms and cell type specificity of PNP transport are not fully understood.

Purpose of the Study:

  • To investigate the epithelial cell type-specificity of PNP trafficking.
  • To elucidate the mechanisms of PNP translocation across Madin Darby canine kidney cell II (MDCK-II) monolayers.

Main Methods:

  • Studied PNP flux across MDCK-II monolayers under various conditions, including calcium chelation, energy depletion, and treatment with endocytosis inhibitors.
  • Utilized confocal laser scanning microscopy to visualize intracellular PNP localization.

Main Results:

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  • Amidine-modified PNP crossed MDCK-II monolayers 500 times faster than carboxylate-modified PNP.
  • PNP translocation decreased significantly with energy depletion and was inhibited by monodansylcadaverine and dynasore, indicating clathrin-mediated endocytosis.
  • PNP colocalized with clathrin heavy chain within cells.

    • Conclusions:

    • PNP translocation across MDCK-II cells occurs via clathrin-mediated endocytosis, dependent on PNP physicochemical properties.
    • Epithelial nanoparticle uptake and trafficking are influenced by both nanoparticle characteristics and the specific epithelial cell type involved.