McCarthy J, Gong X, Nahirney D, Duszyk M, Radomski MW, Polystyrene nanoparticles activate ion transport in human airway epithelial cells, International Journal of Nanomedicine, 2011, 6, 2011, 1343 - 1356
International Journal of Nanomedicine; 2011; 6;
Background: Over the last decade, nanotechnology has provided researchers with new
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 Clchannels
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.
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