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Short and long-term pulmonary response to inhaled nickel hydroxide nanoparticles (nano-Ni(OH)(2), CMD = 40 nm) in C57BL/6 mice was assessed using a whole body exposure system. For short-term studies mice were exposed for 4 h to nominal concentrations of 100, 500, and 1000 mg/m(3). For long-term studies mice were exposed for 5 h/d, 5 d/w, for up to 5 months (m) to a nominal concentration of 100 mg/m(3). Particle morphology, size distribution, chemical composition, solubility, and intrinsic oxidative capacity were determined. Markers of lung injury and inflammation in bronchoalveolar lavage fluid (BALF); histopathology; and lung tissue elemental nickel content and mRNA changes in macrophage inflammatory protein-2 (Mip-2), chemokine ligand 2 (Ccl2), interleukin 1-alpha (Il-1α), and tumor necrosis factor-alpha (Tnf-α) were assessed. Dose-related changes in BALF analyses were observed 24 h after short-term studies while significant changes were noted after 3 m and/or 5 m of exposure (24 h). Nickel content was detected in lung tissue, Ccl2 was most pronouncedly expressed, and histological changes were noted after 5 m of exposure. Collectively, data illustrates nano-Ni(OH)(2) can induce inflammatory responses in C57BL/6 mice.

Mammalian cells take up nanoparticles (NPs) and some NPs increase ROS. We use imaging and measure ROS in parallel to evaluate NP-cell interactions with type I-like alveolar epithelial cells exposed to NPs at 1.2 µg/cm(2) . Titanium dioxide (Ti0(2)), gold (Au), silver (Ag), and manganese (Mn) were internalized by R3-1 cells; copper (Cu) NPs were observed at the cell surface only. TiO(2) and Au did not increase cell death but Mn and Cu did, with surviving cells recovering after initial Cu exposure. Ag NPs caused 80% of R3-1 cells to lift off the slides within one hour. Amplex Red was used to report H(2)O(2) production after exposure to 0.4 µg/cm(2) TiO(2), Au, Cu, Mn and Ag. TiO(2), Au, and Ag caused no significant increase in H(2)O(2) while Cu and Mn increased H(2)O(2). NPs that give up electrons, increase ROS production and cause cell death in R3-1 cells.

Ultraviolet radiation (UVR) skin exposure is a common exogenous insult that can alter skin barrier and immune functions. With the growing presence of nanoparticles (NPs) in consumer goods and technological applications the potential for NPs to contact UVR-exposed skin is increasing. Therefore it is important to understand the effect of UVR on NP skin penetration and the potential for systemic translocation. Previous studies qualitatively showed that UVR skin exposure can increase the penetration of NPs below the stratum corneum. In this work, an in vivo mouse model was used to quantitatively examine the skin penetration of carboxylated (CdSe/ZnS, core/shell) quantum dots (QDs) through intact and UVR barrier-disrupted murine skin by organ Cd mass analysis. Transepidermal water loss was used to measure the magnitude of the skin barrier defect as a function of UVR dose and time post-UVR exposure. QDs were applied to mice 3-4 days post-UVR exposure at the peak of the skin barrier disruption. Our results reveal unexpected trends that suggest these negative-charged QDs can penetrate barrier intact skin and that penetration and systemic transport depends on the QD application time post-UVR exposure. The effect of UVR on skin-resident dendritic cells and their role in the systemic translocation of these QDs are described. Our results suggest that NP skin penetration and translocation may depend on the specific barrier insult and the inflammatory status of the skin.

A method to investigate the dependence of the physicochemical properties of nanoparticles (e.g. size, surface area and crystal phase) on their oxidant generating capacity is proposed and demonstrated for TiO(2) nanoparticles. Gas phase synthesis methods that allow for strict control of size and crystal phase were used to prepare TiO(2) nanoparticles. The reactive oxygen species (ROS) generating capacity of these particles was then measured. The size dependent ROS activity was established using TiO(2) nanoparticles of 9 different sizes (4 - 195 nm) but the same crystal phase. For a fixed total surface area, an S-shaped curve for ROS generation per unit surface area was observed as a function of particle size. The highest ROS activity per unit area was observed for 30 nm particles, and observed to be constant above 30 nm. There was a decrease in activity per unit area as size decreased from 30 nm to 10 nm; and again constant for particles smaller than 10 nm. The correlation between crystal phase and oxidant capacity was established using TiO(2) nanoparticles of 11 different crystal phase combinations but similar size. The ability of different crystal phases of TiO(2) nanoparticles to generate ROS was highest for amorphous, followed by anatase, and then anatase/rutile mixtures, and lowest for rutile samples. Based on evaluation of the entire dataset, important dose metrics for ROS generation are established. Their implications of these ROS studies on biological and toxicological studies using nanomaterials are discussed.

The dispersion in air of nanoparticles of different sizes, materials and morphologies with controlled agglomeration involving aerosol delivery for in vivo and in vitro studies is one of the most difficult challenges in the field of nanoparticle toxicology. We describe here a nanoparticle dispersion system using an electrospray method to deliver airborne nanoparticles (approximately 10-100 nm) with spatial uniformity and controllable particle concentration for in vitro and in vivo studies. With the dispersion method, single nanoparticles (polystyrene latex particles, TiO(2), Au, Mn, quantum dots, and carbon nanotubes) can be delivered to cells and animals via the air. The degree of agglomeration can be controlled by changing the suspension feeding rate to simulate realistic conditions for exposure studies.