Polystyrene nanoparticle trafficking across MDCK-II

Polystyrene nanoparticles (PNP) cross rat alveolar epithelial cell monolayers via non-endocytic transcellular pathways. To evaluate epithelial cell type-specificity of PNP trafficking, we studied PNP flux across Madin Darby canine kidney cell II monolayers (MDCK-II). The effects of calcium chelation (EGTA), energy depletion (sodium azide (NaN3) or decreased temperature), and endocytosis inhibitors methyl-beta-cyclodextrin (MBC), monodansylcadaverine and dynasore were determined. Amidine-modified PNP cross MDCK-II 500 times faster than carboxylate-modified PNP. PNP flux did not increase in the presence of EGTA. PNP flux at 4 C and after treatment with NaN3 decreased 75% and 80%, respectively. MBC exposure did not decrease PNP flux, whereas dansylcadaverine-or dynasore-treated MDCK-II exhibited similar to 80% decreases in PNP flux. Confocal laser scanning microscopy revealed intracellular colocalization of PNP with clathrin heavy chain. These data indicate that PNP translocation across MDCK-II (1) occurs via clathrin-mediated endocytosis and (2) is dependent on PNP physicochemical properties. We conclude that uptake/trafficking of nanoparticles (NPs) into/across epithelia depends both on properties of the NPs and on the specific epithelial cell type. From the Clinical Editor: This basic science study investigates the membrane translocation of polystyrene nanoparticles (PNP) via an epithelial cell monolayer utilizing canine kidney cells. The authors conclude that translocation occurs via clathrin-mediated endocytosis and is dependent on the physicochemical properties of the particular PNP. (C) 2011 Elsevier Inc. All rights reserved.