State of the art toxicological and microscopic assessment of biomedical nanocrystals on the lung in vitro
Due to the ever increasing production of nanosized materials for a variety of novel
applications (e.g. biomedicine), increased research has focused upon understanding the
potential toxicity of these nanomaterials. In order to determine the potential toxicity of
nanoparticles (NPs), it is essential that, in parallel to biochemical and toxicological
testing, their specific route of uptake (if any), as well as their possible and/or subsequent
intracellular localisation is investigated. By using a novel 3D in vitro triple cell co-culture
model of the human epithelial airway barrier (containing epithelial cells and macrophages
(apical-layer) and dendritic cells (basolateral-layer) which has been shown to mimic the
architecture of the lung in vivo , in combination with a novel air-liquid interface cell
exposure system, it is possible to mimic the exposure of NPs to the lung in vitro . Using
both conventional and state-of-the art toxicological tests, in addition to light, laser
scanning (including digital image restoration) and transmission electron microscopy
methods, it has been possible to determine the interaction of both fluorescent (specifically
designed core-shell nanoparticles with shell-embedded fluorophores for use in
biomedicine) and electron dense NPs with the in vitro triple cell co-culture. It has been
observed that the material of the engineered NPs (either gold or iron oxide) has no
significant influence upon the toxicity and intracellular localisation over time. The results
of these studies have shown that despite different compositions, specific NPs intended for
use in biomedical applications, when exposed realistically (exposure
method/concentration/primary contact cells) cause minimal effects to the lung in vitro .