Polystyrene nanoparticles activate ion transport in human airway epithelial cells

J McCarthy1, X Gong2, D Nahirney2, M Duszyk2, MW Radomski11School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 2Department of Physiology, University of Alberta, Edmonton, Alberta, CanadaBackground: Over the last decade, nanotechnology has provide...

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Autores principales:	McCarthy J, Gong X, Nahirney D, Duszyk M, Radomski MW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/398e4b31ddcb43c0ac41d66afb26ee32
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spelling	oai:doaj.org-article:398e4b31ddcb43c0ac41d66afb26ee322021-12-02T02:49:04ZPolystyrene nanoparticles activate ion transport in human airway epithelial cells1176-91141178-2013https://doaj.org/article/398e4b31ddcb43c0ac41d66afb26ee322011-06-01T00:00:00Zhttp://www.dovepress.com/polystyrene-nanoparticles-activate-ion-transport-in-human-airway-epith-a7752https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013J McCarthy1, X Gong2, D Nahirney2, M Duszyk2, MW Radomski11School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 2Department of Physiology, University of Alberta, Edmonton, Alberta, CanadaBackground: Over the last decade, nanotechnology has provided researchers with new nanometer materials, such as nanoparticles, which have the potential to provide new therapies for many lung diseases. In this study, we investigated the acute effects of polystyrene nanoparticles on epithelial ion channel function.Methods: Human submucosal Calu-3 cells that express cystic fibrosis transmembrane conductance regulator (CFTR) and baby hamster kidney cells engineered to express the wild-type CFTR gene were used to investigate the actions of negatively charged 20 nm polystyrene nanoparticles on short-circuit current in Calu-3 cells by Ussing chamber and single CFTR Cl- channels alone and in the presence of known CFTR channel activators by using baby hamster kidney cell patches.Results: Polystyrene nanoparticles caused sustained, repeatable, and concentration-dependent increases in short-circuit current. In turn, these short-circuit current responses were found to be biphasic in nature, ie, an initial peak followed by a plateau. EC50 values for peak and plateau short-circuit current responses were 1457 and 315.5 ng/mL, respectively. Short-circuit current was inhibited by diphenylamine-2-carboxylate, a CFTR Cl- channel blocker. Polystyrene nanoparticles activated basolateral K+ channels and affected Cl- and HCO3- secretion. The mechanism of short-circuit current activation by polystyrene nanoparticles was found to be largely dependent on calcium-dependent and cyclic nucleotide-dependent phosphorylation of CFTR Cl- channels. Recordings from isolated inside-out patches using baby hamster kidney cells confirmed the direct activation of CFTR Cl- channels by the nanoparticles.Conclusion: This is the first study to identify the activation of ion channels in airway cells after exposure to polystyrene-based nanomaterials. Thus, polystyrene nanoparticles cannot be considered as a simple neutral vehicle for drug delivery for the treatment of lung diseases, due to the fact that they may have the ability to affect epithelial cell function and physiological processes on their own.Keywords: CFTR, cystic fibrosis transmembrane conductance regulator, ion channels, K+ channels, lung cells, polystyrene nanoparticle&nbsp;McCarthy JGong XNahirney DDuszyk MRadomski MWDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 1343-1356 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 McCarthy J Gong X Nahirney D Duszyk M Radomski MW Polystyrene nanoparticles activate ion transport in human airway epithelial cells
description	J McCarthy1, X Gong2, D Nahirney2, M Duszyk2, MW Radomski11School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 2Department of Physiology, University of Alberta, Edmonton, Alberta, CanadaBackground: Over the last decade, nanotechnology has provided researchers with new nanometer materials, such as nanoparticles, which have the potential to provide new therapies for many lung diseases. In this study, we investigated the acute effects of polystyrene nanoparticles on epithelial ion channel function.Methods: Human submucosal Calu-3 cells that express cystic fibrosis transmembrane conductance regulator (CFTR) and baby hamster kidney cells engineered to express the wild-type CFTR gene were used to investigate the actions of negatively charged 20 nm polystyrene nanoparticles on short-circuit current in Calu-3 cells by Ussing chamber and single CFTR Cl- channels alone and in the presence of known CFTR channel activators by using baby hamster kidney cell patches.Results: Polystyrene nanoparticles caused sustained, repeatable, and concentration-dependent increases in short-circuit current. In turn, these short-circuit current responses were found to be biphasic in nature, ie, an initial peak followed by a plateau. EC50 values for peak and plateau short-circuit current responses were 1457 and 315.5 ng/mL, respectively. Short-circuit current was inhibited by diphenylamine-2-carboxylate, a CFTR Cl- channel blocker. Polystyrene nanoparticles activated basolateral K+ channels and affected Cl- and HCO3- secretion. The mechanism of short-circuit current activation by polystyrene nanoparticles was found to be largely dependent on calcium-dependent and cyclic nucleotide-dependent phosphorylation of CFTR Cl- channels. Recordings from isolated inside-out patches using baby hamster kidney cells confirmed the direct activation of CFTR Cl- channels by the nanoparticles.Conclusion: This is the first study to identify the activation of ion channels in airway cells after exposure to polystyrene-based nanomaterials. Thus, polystyrene nanoparticles cannot be considered as a simple neutral vehicle for drug delivery for the treatment of lung diseases, due to the fact that they may have the ability to affect epithelial cell function and physiological processes on their own.Keywords: CFTR, cystic fibrosis transmembrane conductance regulator, ion channels, K+ channels, lung cells, polystyrene nanoparticle&nbsp;
format	article
author	McCarthy J Gong X Nahirney D Duszyk M Radomski MW
author_facet	McCarthy J Gong X Nahirney D Duszyk M Radomski MW
author_sort	McCarthy J
title	Polystyrene nanoparticles activate ion transport in human airway epithelial cells
title_short	Polystyrene nanoparticles activate ion transport in human airway epithelial cells
title_full	Polystyrene nanoparticles activate ion transport in human airway epithelial cells
title_fullStr	Polystyrene nanoparticles activate ion transport in human airway epithelial cells
title_full_unstemmed	Polystyrene nanoparticles activate ion transport in human airway epithelial cells
title_sort	polystyrene nanoparticles activate ion transport in human airway epithelial cells
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/398e4b31ddcb43c0ac41d66afb26ee32
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Polystyrene nanoparticles activate ion transport in human airway epithelial cells

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