Nanoparticle translocation across mouse alveolar epithelial cell monolayers: species-specific mechanisms.

UNLABELLED Studies of polystyrene nanoparticle (PNP) trafficking across mouse alveolar epithelial cell monolayers (MAECM) show apical-to-basolateral flux of 20 and 120nm amidine-modified PNP is ~65 times faster than that of 20 and 100nm carboxylate-modified PNP, respectively. Calcium chelation with EGTA has little effect on amidine-modified PNP flux, but increases carboxylate-modified PNP flux ~50-fold. PNP flux is unaffected by methyl-β-cyclodextrin, while ~70% decrease in amidine- (but not carboxylate-) modified PNP flux occurs across chlorpromazine- or dynasore-treated MAECM. Confocal microscopy reveals intracellular amidine- and carboxylate-modified PNP and association of amidine- (but not carboxylate-) modified PNP with clathrin heavy chain. These data indicate (1) amidine-modified PNP translocate across MAECM primarily via clathrin-mediated endocytosis and (2) physicochemical properties (e.g., surface charge) determine PNP interactions with mouse alveolar epithelium. Uptake/trafficking of nanoparticles into/across epithelial barriers is dependent on both nanoparticle physicochemical properties and (based on comparison with our prior results) specific epithelial cell type. FROM THE CLINICAL EDITOR In this study of polystyrene nanoparticle trafficking across mouse alveolar epithelial cell monolayers, the authors determined that uptake/trafficking of nanoparticles into/across epithelial barriers is dependent on both nanoparticle physicochemical properties and the specific type of epithelial cells.

[1]  M. Matthay,et al.  Alveolar epithelial transport. Basic science to clinical medicine. , 2001, American journal of respiratory and critical care medicine.

[2]  E R Weibel,et al.  Morphometry of the human pulmonary acinus , 1988, The Anatomical record.

[3]  K. Landfester,et al.  Uptake mechanism of oppositely charged fluorescent nanoparticles in HeLa cells. , 2008, Macromolecular bioscience.

[4]  H. McMahon,et al.  Mechanisms of endocytosis. , 2009, Annual review of biochemistry.

[5]  V. Grassian,et al.  Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model , 2011, Particle and Fibre Toxicology.

[6]  Tsun-Jen Cheng,et al.  Pulmonary toxicity of inhaled nanoscale and fine zinc oxide particles: Mass and surface area as an exposure metric , 2011, Inhalation toxicology.

[7]  Nicklas Raun Jacobsen,et al.  Biodistribution of gold nanoparticles in mouse lung following intratracheal instillation , 2009, Chemistry Central journal.

[8]  Jürgen Seitz,et al.  Size dependence of the translocation of inhaled iridium and carbon nanoparticle aggregates from the lung of rats to the blood and secondary target organs , 2009, Inhalation toxicology.

[9]  H. Bohidar,et al.  Interaction of soot derived multi-carbon nanoparticles with lung surfactants and their possible internalization inside alveolar cavity. , 2010, Indian journal of experimental biology.

[10]  M. D. Martins,et al.  Glycocalyx of lung epithelial cells. , 2002, International review of cytology.

[11]  A. Shimada,et al.  Translocation Pathway of the Intratracheally Instilled Ultrafine Particles from the Lung into the Blood Circulation in the Mouse , 2006, Toxicologic pathology.

[12]  E. Crandall,et al.  Reactivity of alveolar epithelial cells in primary culture with type I cell monoclonal antibodies. , 1992, American journal of respiratory cell and molecular biology.

[13]  P. Sansonetti,et al.  Shigella flexneri enters human colonic Caco-2 epithelial cells through the basolateral pole , 1992, Infection and immunity.

[14]  B. Hirst,et al.  Paracellular barrier and junctional protein distribution depend on basolateral extracellular Ca2+ in cultured epithelia. , 1994, Biochimica et biophysica acta.

[15]  D. Defouw Ultrastructural features of alveolar epithelial transport. , 1983, The American review of respiratory disease.

[16]  T. Kirchhausen,et al.  Dynasore, a cell-permeable inhibitor of dynamin. , 2006, Developmental cell.

[17]  Y. Schneider,et al.  Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on cellular metabolism at realistic intestinal concentrations. , 2006, Toxicology letters.

[18]  H. Galla,et al.  Monolayers of porcine alveolar epithelial cells in primary culture as an in vitro model for drug absorption studies. , 2007, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[19]  T. Sandström,et al.  Adverse cardiovascular effects of air pollution , 2009, Nature Clinical Practice Cardiovascular Medicine.

[20]  R. Parton,et al.  Lipid Rafts and Caveolae as Portals for Endocytosis: New Insights and Common Mechanisms , 2003, Traffic.

[21]  Heinz Fehrenbach,et al.  Alveolar epithelial type II cell: defender of the alveolus revisited , 2001, Respiratory research.

[22]  J. Samet,et al.  Air Pollution and Cardiovascular Disease: A Statement for Healthcare Professionals From the Expert Panel on Population and Prevention Science of the American Heart Association , 2004, Circulation.

[23]  W G Kreyling,et al.  Distribution Pattern of Inhaled Ultrafine Gold Particles in the Rat Lung , 2006, Inhalation toxicology.

[24]  S. Hamm-Alvarez,et al.  Polystyrene nanoparticle trafficking across alveolar epithelium. , 2008, Nanomedicine : nanotechnology, biology, and medicine.

[25]  G. Oberdörster,et al.  Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles , 2005, Environmental health perspectives.

[26]  D. Frazer,et al.  Nanoparticle Inhalation Impairs Coronary Microvascular Reactivity via a Local Reactive Oxygen Species-Dependent Mechanism , 2010, Cardiovascular Toxicology.

[27]  Brian J. Bennett,et al.  Ambient Particulate Pollutants in the Ultrafine Range Promote Early Atherosclerosis and Systemic Oxidative Stress , 2008, Circulation research.

[28]  Wolfgang Kreyling,et al.  Ultrafine Particles Cross Cellular Membranes by Nonphagocytic Mechanisms in Lungs and in Cultured Cells , 2005, Environmental health perspectives.

[29]  Annette Peters,et al.  Translocation and potential neurological effects of fine and ultrafine particles a critical update , 2006, Particle and Fibre Toxicology.

[30]  S. Hamm-Alvarez,et al.  Translocation of PEGylated quantum dots across rat alveolar epithelial cell monolayers , 2011, International journal of nanomedicine.

[31]  W. D. de Jong,et al.  Drug delivery and nanoparticles: Applications and hazards , 2008, International journal of nanomedicine.

[32]  J. M. Cheek,et al.  Tight monolayers of rat alveolar epithelial cells: bioelectric properties and active sodium transport. , 1989, The American journal of physiology.

[33]  R. Senior,et al.  Characterization of mouse alveolar epithelial cell monolayers. , 2009, American journal of physiology. Lung cellular and molecular physiology.

[34]  Simon Benita,et al.  Surface charge of nanoparticles determines their endocytic and transcytotic pathway in polarized MDCK cells. , 2008, Biomacromolecules.

[35]  W. Kreyling,et al.  The influence of pulmonary surfactant on nanoparticulate drug delivery systems. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[36]  A. Yu,et al.  Polystyrene nanoparticle trafficking across MDCK-II. , 2011, Nanomedicine : nanotechnology, biology, and medicine.

[37]  Feng Zhao,et al.  The translocation of fullerenic nanoparticles into lysosome via the pathway of clathrin-mediated endocytosis , 2008, Nanotechnology.

[38]  Michael Lipsett,et al.  A Statement for Healthcare Professionals From the Expert Panel on Population and Prevention Science of the American Heart Association , 2004 .

[39]  Yuliang Zhang,et al.  Transmembrane delivery of the cell-penetrating peptide conjugated semiconductor quantum dots. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[40]  Simon Benita,et al.  Targeting of nanoparticles to the clathrin-mediated endocytic pathway. , 2007, Biochemical and biophysical research communications.

[41]  L. Malerød,et al.  Clathrin-dependent endocytosis. , 2004, The Biochemical journal.

[42]  R T Borchardt,et al.  Paracellular diffusion in Caco-2 cell monolayers: effect of perturbation on the transport of hydrophilic compounds that vary in charge and size. , 1997, Journal of pharmaceutical sciences.

[43]  B. Jasani,et al.  Caveolin and its cellular and subcellular immunolocalisation in lung alveolar epithelium: implications for alveolar epithelial type I cell function , 1999, Cell and Tissue Research.

[44]  R. Matran,et al.  Characterization of endocytosis and exocytosis of cationic nanoparticles in airway epithelium cells , 2010, Nanotechnology.

[45]  Iseult Lynch,et al.  Quantitative assessment of the comparative nanoparticle-uptake efficiency of a range of cell lines. , 2011, Small.

[46]  P. Artursson,et al.  Transport of nanoparticles across an in vitro model of the human intestinal follicle associated epithelium. , 2005, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[47]  J. M. Cheek,et al.  Type I cell-like morphology in tight alveolar epithelial monolayers. , 1989, Experimental cell research.

[48]  A. Ivanov,et al.  Pharmacological inhibition of endocytic pathways: is it specific enough to be useful? , 2008, Methods in molecular biology.

[49]  Noah Malmstadt,et al.  Mechanisms of alveolar epithelial translocation of a defined population of nanoparticles. , 2010, American journal of respiratory cell and molecular biology.

[50]  S. Thakur,et al.  Emerging Implications of Nanotechnology on Cancer Diagnostics and Therapeutics , 2012 .

[51]  Robert Langer,et al.  Impact of nanotechnology on drug delivery. , 2009, ACS nano.