Decreased Dissolution of ZnO by Iron Doping Yields Nanoparticles with Reduced Toxicity in the Rodent Lung and Zebrafish Embryos

Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, California 90095, USA.
ACS Nano (Impact Factor: 12.88). 02/2011; 5(2):1223-35. DOI: 10.1021/nn1028482
Source: PubMed


We have recently shown that the dissolution of ZnO nanoparticles and Zn(2+) shedding leads to a series of sublethal and lethal toxicological responses at the cellular level that can be alleviated by iron doping. Iron doping changes the particle matrix and slows the rate of particle dissolution. To determine whether iron doping of ZnO also leads to lesser toxic effects in vivo, toxicity studies were performed in rodent and zebrafish models. First, we synthesized a fresh batch of ZnO nanoparticles doped with 1-10 wt % of Fe. These particles were extensively characterized to confirm their doping status, reduced rate of dissolution in an exposure medium, and reduced toxicity in a cellular screen. Subsequent studies compared the effects of undoped to doped particles in the rat lung, mouse lung, and the zebrafish embryo. The zebrafish studies looked at embryo hatching and mortality rates as well as the generation of morphological defects, while the endpoints in the rodent lung included an assessment of inflammatory cell infiltrates, LDH release, and cytokine levels in the bronchoalveolar lavage fluid. Iron doping, similar to the effect of the metal chelator, DTPA, interfered in the inhibitory effects of Zn(2+) on zebrafish hatching. In the oropharyngeal aspiration model in the mouse, iron doping was associated with decreased polymorphonuclear cell counts and IL-6 mRNA production. Doped particles also elicited decreased heme oxygenase 1 expression in the murine lung. In the intratracheal instillation studies in the rat, Fe doping was associated with decreased polymorphonuclear cell counts, LDH, and albumin levels. All considered, the above data show that Fe doping is a possible safe design strategy for preventing ZnO toxicity in animals and the environment.

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    • "The authors attributed the reduced toxicity of Fe@ZnO NPs to lesser dissolution in the growth media [25]. The extent of dissolution decreases (>30% in case of 10% Fe doping) with increase in the amount of Fe compared to that of ZnO NPs [25]. Conversely, Li et al. reported no correlation between the IC 50 (half maximal inhibitory concentration) values and percentage of iron doping of Fe@ZnO in Bacillus subtilis, Escherichia coli, and Pseudomonas putida in aquatic media. "
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    • "For example, 0.405 mg/L Zn 2+ was initially released from 1 mg/L nZnO (Bai et al. 2010), over 25% of Zn 2+ dissolved from 50 mg/L nZnO (Xia et al. 2011) and 1 mg/L dissolution from 10 mg/L ZnO (Zhu et al. 2009). Limiting NP dissolution via capping or doping methods are being explored to abrogate the effects caused by free metal toxicity (Xia et al. 2011). It is not clear whether delayed hatch can be attributed to the NPs or to the free metal dissolved from the NPs, therefore identifying the active species is of paramount importance. "
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