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WIREs Nanomed Nanobiotechnol
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Physicochemical factors that affect metal and metal oxide nanoparticle passage across epithelial barriers

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Abstract The diversity of nanomaterials in terms of size, shape, and surface chemistry poses a challenge to those who are trying to characterize the human health and environmental risks associated with incidental and unintentional exposures. There are numerous products that are already commercially available that contain solid metal and metal oxide nanoparticles, either embedded in a matrix or in solution. Exposure assessments for these products are often incomplete or difficult due to technological challenges associated with detection and quantitation of nanoparticles in gaseous or liquid carriers. The main focus of recent research has been on hazard identification. However, risk is a product of hazard and exposure, and one significant knowledge gap is that of the target organ dose following in vivo exposures. In order to reach target organs, nanoparticles must first breach the protective barriers of the respiratory tract, gastrointestinal tract, or skin. The fate of those nanoparticles that reach physiological barriers is in large part determined by the properties of the particles and the barriers themselves. This article reviews the physiological properties of the lung, gut, and skin epithelia, the physicochemical properties of metal and metal oxide nanoparticles that are likely to affect their ability to breach epithelial barriers, and what is known about their fate following in vivo exposures. Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

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Deposition of particles in the respiratory tract as a function of their size, with inset illustrating the proximity of the air spaces (alveoli) to the vasculature (in pink). (Reprinted with permission and adapted from Ref 7. Copyright Environmental Health Perspectives).

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TEM images of (top) a corneocyte, illustrating the dense cornified envelope feature and (bottom) a skin section, illustrating corneocytes in the stratum corneum (SC) and granules in the stratum granulosum (SG) (extends beyond what is shown). Black spots are silver‐enhanced quantum dots that penetrated the SC following application to UV‐irradiated mouse skin (see Mortensen et al., 2008, for details).

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Possible routes of NP uptake in GI tract include tight junctions (paracellular), dendritic cells, and transcytosis. Inset shows phase contrast (right) and confocal (left) images of FAE, with only the M cells taking up and transporting antigen (Ulex europeaus), in this case bound to 0.5 µm Fluoresbrite microspheres. Enterocytes (yellow arrows) do not take up antigen.

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