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Translocation of functionalized multi-walled carbon nanotubes across human pulmonary alveolar epithelium: dominant role of epithelial type 1 cells

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Title: Translocation of functionalized multi-walled carbon nanotubes across human pulmonary alveolar epithelium: dominant role of epithelial type 1 cells
Authors: Ruenraromgsak, P
Chen, S
Hu, S
Melbourne, J
Sweeney, S
Thorley, AJ
Skepper, JN
Shaffer, MSP
Tetley, TD
Porter, AE
Item Type: Journal Article
Abstract: Uptake and translocation of short functionalized multi-walled carbon nanotubes (short-fMWCNTs) through the pulmonary respiratory epithelial barrier depend on physicochemical property and cell type. Two monoculture models, immortalized human alveolar epithelial type 1 (TT1) cells and primary human alveolar epithelial type 2 cells (AT2), which constitute the alveolar epithelial barrier, were employed to investigate the uptake and transport of 300 and 700 nm in length, poly(4-vinylpyridine)-functionalized, multi-walled carbon nanotubes (p(4VP)-MWCNTs) using quantitative imaging and spectroscopy techniques. The p(4VP)-MWCNT exhibited no toxicity on TT1 and AT2 cells, but significantly decreased barrier integrity (*p < 0.01). Uptake of p(4VP)-MWCNTs was observed in 70% of TT1 cells, correlating with compromised barrier integrity and basolateral p(4VP)-MWCNT translocation. There was a small but significantly greater uptake of 300 nm p(4VP)-MWCNTs than 700 nm p(4VP)-MWCNTs by TT1 cells. Up to 3% of both the 300 and 700 nm p(4VP)-MWCNTs reach the basal chamber; this relatively low amount arose because the supporting transwell membrane minimized the amount of p(4VP)-MWCNT translocating to the basal chamber, seen trapped between the basolateral cell membrane and the membrane. Only 8% of AT2 cells internalized p(4VP)-MWCNT, accounting for 17% of applied p(4VP)-MWCNT), with transient effects on barrier function, which initially fell then returned to normal; there was no MWCNT basolateral translocation. The transport rate was MWCNT length modulated. The comparatively lower p(4VP)-MWCNT uptake by AT2 cells is proposed to reflect a primary barrier effect of type 2 cell secretions and the functional differences between the type 1 and type 2 alveolar epithelial cells.
Issue Date: 24-Apr-2016
Date of Acceptance: 1-Apr-2016
URI: http://hdl.handle.net/10044/1/69227
DOI: https://dx.doi.org/10.1021/acsnano.5b08218
ISSN: 1936-086X
Publisher: American Chemical Society
Start Page: 5070
End Page: 5085
Journal / Book Title: ACS Nano
Volume: 10
Issue: 5
Copyright Statement: © 2016 American Chemical Society
Sponsor/Funder: The Leverhulme Trust
Medical Research Council (MRC)
National Institutes of Health
Commission of the European Communities
Funder's Grant Number: F/07 058/BT
G0700926
H50669
ERC-2010-StG-20091028
Keywords: Science & Technology
Physical Sciences
Technology
Chemistry, Multidisciplinary
Chemistry, Physical
Nanoscience & Nanotechnology
Materials Science, Multidisciplinary
Chemistry
Science & Technology - Other Topics
Materials Science
functionalized multi-walled carbon nanotubes
uptake
translocation
alveolar epithelial barrier
electron microscopy
quantitative imaging technique
POLYSTYRENE NANOPARTICLE TRAFFICKING
ORAL-DRUG DELIVERY
SURFACTANT LIPIDS
TRANS LOCATION
STEM-CELLS
LUNG
AGGREGATION
TOXICITIES
INHALATION
ADSORPTION
Cell Culture Techniques
Epithelial Cells
Humans
Lung
Nanotubes, Carbon
Pulmonary Alveoli
Respiratory Mucosa
MD Multidisciplinary
Publication Status: Published
Online Publication Date: 2016-04-01
Appears in Collections:Materials
Chemistry
National Heart and Lung Institute
Airway Disease
Faculty of Medicine
Faculty of Natural Sciences



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