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WIREs Nanomed Nanobiotechnol
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Nanotoxicology: a personal perspective

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Abstract Nanoparticles arise from a wide variety of natural and man‐made sources and have a diverse array of biological, chemical, and physical properties. The toxicity of these particles can be roughly divided into two categories: 1) the enhanced delivery of toxic agents 2) toxicity induced the properties of the particle itself. The use of nanoparticles to provide enhanced delivery of chemotherapeutics is presented followed by a discussion of the size‐based effects of electron transfer and physical membrane disruption. Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

Poly(amidoamine) (PAMAM) dendrimer interactions with biological membranes. Left panel: Atomic force microscopy (AFM) observation of dimyristoylphoshatidylcholine (DMPC) supported lipid bilayers (a), (c), and (e) before and after incubation with (b) G7‐NH2, (d) G5‐NH2, and (f) G5‐Ac PAMAM dendrimers, respectively. Middle panel: Space‐filling models of chemical structures of (a) G7‐NH2, (b) G5‐NH2, and (c) G5‐Ac PAMAM dendrimers. Right panel: Lactate dehydrogenase (LDH) leakage as a result of cell exposure to PAMAM dendrimers. (a) Size effect of G7‐NH2 and G5‐NH2 on the LDH leakage out of KB and Rat2 cells after incubation at 37°C for 3 h and (b) surface group dependency on the LDH leakage at different temperatures. Note that larger dendrimers (G7‐NH2) induce formation of new nanoscale holes in the bilayers as seen in the AFM images and cause more amount of LDH leakage out of live cells than G5‐NH2. G5‐NH2 dendrimers do not cause new hole formation in the lipid bilayers but instead expand preexisting defects. In contrast, G5‐Ac dendrimers do not cause hole formation, expansion of preexisting defects, or LDH leakage out of live cells. (Reprinted with permission from Ref 33. Copyright 2007 American Chemical Society) .

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Confocal scanning microscopy of porcine skin treated with QD 565 for 8 h. (a‐c) QD‐PEG; (d‐f) QD‐PEG‐NH2; (g‐i) QD‐COOH. DIC channel (a, d, g) provides an unobstructed view of the skin layers. Confocal‐DIC overlay with the green QD fluorescence channel (b, e, h) shows QD localization within the epidermis or dermis (arrows). Fluorescence intensity scan of the QD emission (c, f, i). QD 565 are localized in the epidermal (PEG and COOH coatings) or dermal (NH2 coating) layers by 8 h. Scale bars equal 50 µm. (Figure revised with permission from Ref 47. Copyright 2006 Oxford Press).

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(a) A snapshot at the beginning (0 ns) of the simulation of system G5‐1 (100% acetylated). Snapshots at the end (0.5 µs) of simulations of systems (b) G5‐1, (c) G5‐2 (50% acetylated), (d) G5‐3 (un‐acetylated), (e) G5‐4 (un‐acetylated, 500 mM NaCl), (f) G5‐5 (un‐acetylated, low temperature), (g) G3‐1 (100% acetylated), and (h) G3‐2 (un‐acetylated). Black dots represent dendrimers, and blue dots represent head groups of the dipalmitoylphosphatidyl choline bilayer. The explicit water and ions are omitted for clarity. The images were created with visual molecular dynamics (VMD). (Reprinted with permission from Ref 42. Copyright 2006 Americal Chemical Society).

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