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Title: An investigation of the carbon nanotube-lipid interface and its impact upon lung function
Author: Melbourne, Jodie
ISNI:       0000 0004 7233 0797
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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Multiwalled carbon nanotubes (MWCNTs) are now synthesized on a scale of thousands of tonnes per year, creating a considerable inhalation risk for the people that work with them. However, significant knowledge gaps on MWCNT pulmonary toxicity still remain due to the complex composition of the air-lung interface, particularly the influence of the pulmonary surfactant (PS) which coats the surface of the lung, plus a lack of insight into the impact of MWCNT physicochemical properties on their toxicity. The aims of this thesis were two-fold. Firstly, the Langmuir Blodgett trough was used to investigate the impact of MWCNT inhalation on the biophysical behaviour of PS lipids at the air-water interface. Changes were found to be length-dependant. ‘Short’ MWCNTs (1.1 μm, SD = 0.61) reduced the maximum interfacial film pressure by 10 mN/m (14%) in dipalmitoylphosphatidylcholine (DPPC) and PS, at an interfacial MWCNT-PS lipid mass ratio range of 50:1 to 1:1. ‘Long’ commercial MWCNTs (2.1 μm, SD = 1.2) caused compression resistance at the same mass loadings. ‘Very long’ MWCNTs (35 μm, SD = 19) sequestered DPPC and were squeezed out of the film. Positive and neutral functionalised hydrophilic MWCNTs also caused significant monolayer expansion. In a complementary imaging study, ordered DPPC coronas were found to form on the MWCNT surface. MWCNT aspect ratio and charge can therefore both influence the compression resistance and maximum pressure of PS lipids, each believed to influence PS function. Secondly, 6 popular commercial MWCNT types were characterised, and their toxicity to alveolar macrophage cells (AMs) investigated. The MWCNTs shared some similar characteristics: all MWCNTs contained only iron and carbon, diameters were 10-25 nm, the D/G ratios were ~1, and the measured agglomerate sizes in cell culture medium were 0.26-0.39 μm^2. However, the samples displayed different cytotoxicities, with 4 samples causing significant reductions in AM viability. Imaging of critical point dried cells, using field ion beam scanning electron microscopy, showed that the AMs tended to surround and engulf MWCNT agglomerates. The more toxic MWCNTs were associated with lower cell numbers and signs of an inability of the AMs to phagocytose the MWCNT agglomerates. Certain classes of commercial MWCNTs therefore pose a threat to lung health if inhaled. Further investigations are needed to understand which of their characteristics cause increased toxicity.
Supervisor: Porter, Alexandra ; Shaffer, Milo Sponsor: Leverhulme Trust ; European Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral