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4 February 2011 State of the art toxicological and microscopic assessment of biomedical nanocrystals on the lung in vitro
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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.
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Martin J. D. Clift, Peter Gehr, and Barbara Rothen-Rutishauser "State of the art toxicological and microscopic assessment of biomedical nanocrystals on the lung in vitro", Proc. SPIE 7909, Colloidal Quantum Dots/Nanocrystals for Biomedical Applications VI, 790909 (4 February 2011);

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