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WIREs Nanomed Nanobiotechnol
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Metal‐based nanoparticles and their toxicity assessment

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Abstract Nanoparticles (NPs) can potentially cause adverse effects on organ, tissue, cellular, subcellular, and protein levels due to their unusual physicochemical properties (e.g., small size, high surface area to volume ratio, chemical composition, crystallinity, electronic properties, surface structure reactivity and functional groups, inorganic or organic coatings, solubility, shape, and aggregation behavior). Metal NPs, in particular, have received increasing interest due to their widespread medical, consumer, industrial, and military applications. However, as particle size decreases, some metal‐based NPs are showing increased toxicity, even if the same material is relatively inert in its bulk form (e.g., Ag, Au, and Cu). NPs also interact with proteins and enzymes within mammalian cells and they can interfere with the antioxidant defense mechanism leading to reactive oxygen species generation, the initiation of an inflammatory response and perturbation and destruction of the mitochondria causing apoptosis or necrosis. As a result, there are many challenges to overcome before we can determine if the benefits outweigh the risks associated with NPs. WIREs Nanomed Nanobiotechnol 2010 2 544–568 This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

Microscopic observation of Al2O3 nanoparticles (NPs) and Al NPs phagocytized by alveolar macrophages (AM). Various representative images (a–f) were taken during phagocytosis with the Olympus IX71 inverted fluorescent microscope attached with an advanced high illuminating system. Cells were exposed to Al2O3NPs and Al NPs at 5 or 25 µg/mL for 24 h. Fluorescent latex beads (2 µm) were given to the cells after exposure. The beads appear as bright globular areas in the cells and were dosed at a 10:1 ratio (10 beads for every cell) for 6 h. Macrophages and beads phagocytized by macrophages were counted to obtain a phagocytosis index (PI). PI defined as % macrophages that take in beads × average number of beads taken in by a positive macrophage. (a) No exposure to Al NPs (control); (b) AM exposed to 25 µg/mL of Al2O3 NPs 30 nm; (c) AM exposed to 25 µg/mL of Al2O3NPs 40 nm; (d) AM exposed to 5 µg/mL of Al NPs 50 nm; (e) AM exposed to 5 µg/mL of Al NPs 80 nm; (f) AM exposed to 5 µg/mL of Al NP 120 nm. Yellow arrows indicate the uptake of fluorescent latex beads. Blue arrows indicate the Al particles uptake (Reprinted with permission from Ref 108. Copyright 2007 IOP Publishing).

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Microscopic observation of the cells treated with cerium oxide nanoparticles. Aggregates of cerium oxide nanoparticles with bright microscopic images were localized in the perinuclear region of nucleus. The images of aggregates were enlarged with the increase in exposure time to form a ring like shape. Arrows show the aggregates of cerium oxide nanoparticles in the cells (Reprinted with permission from Ref 146. Copyright 2008 Elsevier).

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Titanium concentration in different tissue types of female mice 2 weeks post‐exposure. Varying sizes of titanium dioxide (TiO2) nanoparticles (NPs) were administered. * Represents significant difference from the control group (Dennett's, p < 0.05), and + represents significant difference from the fine 155 nm TiO2 group (Student's, p < 0.05) (Reprinted with permission from Ref 148. Copyright 2007 Elsevier).

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Micrographs showing gill injury induced by 48 h copper exposure. Soluble copper and nanocopper induced [sic] dramatic changes in gill morphology. Clockwise from top left: Control, 0.25 mg/L soluble Cu2+, 1.5 mg/L nanocopper, 0.25 mg/L nanocopper (Reprinted with permission from Ref 138. Copyright 2007 American Chemical Society).

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(A) The appearance of mouse kidneys in various treatment groups: (a) micro‐Cu (1077 mg/kg), (b) nano‐Cu (1080 mg/kg) and (c) the control. (B) The appearance of mouse spleens in various treatment groups: (a) micro‐Cu (1077 mg/kg), (b) nano‐Cu (1080 mg/kg) and (c) the control (Reprinted with permission from Ref 135. Copyright 2006 IOP Publishing).

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Transmission electron microscopy images of ultrathin sections of the zebrafish embryos treated with 25 µg/mL of Ag‐BSA nanoparticles (NPs). (a) Deposition of the Ag NPs in the cytoplasm and (b) nucleus of the cells near the trunk and tail, respectively. Images were captured using a JEOL JSM 3010F. The nucleus is indicated by ‘n’ and cytoplasm by ‘c’. (c) Magnified images of the nucleus show NP deposition. (d) Clumps of NPs were seen near the epithelium. (e) Low magnification images of the heart, showing dark spots containing NPs. (f) Magnified images from heart confirming the presence of NPs. The lattice plane identifies NPs. (g) Sections of brain showing the presence of NPs. (h) EDS of embryos showing the presence of Ag (Reprinted with permission from Ref 132. Copyright 2008 IOP Publishing Limited).

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Electron microscopy characterization of hydrocarbon‐processed 25 nm silver nanoparticles (Ag25) and polysaccharide‐coated silver nanoparticles (Ag25Disp). (a–c) Ag25 and (f–h) Ag25Disp. (a, f) Scanning electron microscope images with scale bars 100 nm; (b, g) transmission electron microscope images with scale bars 20 nm; (c, d) selected area diffraction patterns (Reprinted with permission from Ref 128. Copyright 2008 IOP Publishing Limited).

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