title: Translocation of PEGylated quantum dots across rat alveolar epithelial cell monolayers.
abstract: BACKGROUND
  In this study, primary rat alveolar epithelial cell monolayers (RAECM) were used to investigate transalveolar epithelial quantum dot trafficking rates and underlying transport mechanisms.
  
  
  METHODS
  Trafficking rates of quantum dots (PEGylated CdSe/ZnS, core size 5.3 nm, hydrodynamic size 25 nm) in the apical-to-basolateral direction across RAECM were determined. Changes in bioelectric properties (ie, transmonolayer resistance and equivalent active ion transport rate) of RAECM in the presence or absence of quantum dots were measured. Involvement of endocytic pathways in quantum dot trafficking across RAECM was assessed using specific inhibitors (eg, methyl-β-cyclodextrin, chlorpromazine, and dynasore for caveolin-, clathrin-, and dynamin-mediated endocytosis, respectively). The effects of lowering tight junctional resistance on quantum dot trafficking were determined by depleting Ca(2+) in apical and basolateral bathing fluids of RAECM using 2 mM EGTA. Effects of temperature on quantum dot trafficking were studied by lowering temperature from 37°C to 4°C.
  
  
  RESULTS
  Apical exposure of RAECM to quantum dots did not elicit changes in transmonolayer resistance or ion transport rate for up to 24 hours; quantum dot trafficking rates were not surface charge-dependent; methyl-β-cyclodextrin, chlorpromazine, and dynasore did not decrease quantum dot trafficking rates; lowering of temperature decreased transmonolayer resistance by approximately 90% with a concomitant increase in quantum dot trafficking by about 80%; and 24 hours of treatment of RAECM with EGTA decreased transmonolayer resistance by about 95%, with increased quantum dot trafficking of up to approximately 130%.
  
  
  CONCLUSIONS
  These data indicate that quantum dots do not injure RAECM and that quantum dot trafficking does not appear to take place via endocytic pathways involving caveolin, clathrin, or dynamin. We conclude that quantum dot translocation across RAECM takes place via both transcellular and paracellular pathways and, based on comparison with our prior studies, interactions of nanoparticles with RAECM are strongly dependent on nanoparticle composition and surface properties.
authors: Will Rogers Institute Pulmonary Research Center, University of Southern California, Los Angeles, CA, USA.
authors: Farnoosh
authors: F
authors: Fazlollahi
authors: Arnold
authors: A
authors: Sipos
authors: Yong Ho
authors: YH
authors: Kim
authors: Sarah F
authors: SF
authors: Hamm-Alvarez
authors: Zea
authors: Z
authors: Borok
authors: Kwang-Jin
authors: KJ
authors: Kim
authors: Edward D
authors: ED
authors: Crandall
mesh_terms: D000818:Animals; D019187:Cadmium Compounds / Q000737:chemistry; D002746:Chlorpromazine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006835:Hydrazones / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D018613:Microscopy, Confocal; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology; D045663:Quantum Dots; D051381:Rats; D018036:Selenium Compounds / Q000737:chemistry; D013440:Sulfides / Q000737:chemistry; D013696:Temperature; D017967:Zinc Compounds / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D019187:Cadmium Compounds; D006835:Hydrazones; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D018036:Selenium Compounds; D013440:Sulfides; D017967:Zinc Compounds; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D011092:Polyethylene Glycols; D004533:Egtazic Acid; C058667:cadmium selenide; C031238:zinc sulfide; D002746:Chlorpromazine