Use of Metal Oxide Nanoparticle Band Gap To Develop a Predictive Paradigm for Oxidative Stress and Acute Pulmonary Inflammation

California NanoSystems Institute, University of California, Los Angeles, California 90095-1680, USA.
ACS Nano (Impact Factor: 12.88). 04/2012; 6(5):4349-68. DOI: 10.1021/nn3010087
Source: PubMed


We demonstrate for 24 metal oxide (MOx) nanoparticles that it is possible to use conduction band energy levels to delineate their toxicological potential at cellular and whole animal levels. Among the materials, the overlap of conduction band energy (E(c)) levels with the cellular redox potential (-4.12 to -4.84 eV) was strongly correlated to the ability of Co(3)O(4), Cr(2)O(3), Ni(2)O(3), Mn(2)O(3), and CoO nanoparticles to induce oxygen radicals, oxidative stress, and inflammation. This outcome is premised on permissible electron transfers from the biological redox couples that maintain the cellular redox equilibrium to the conduction band of the semiconductor particles. Both single-parameter cytotoxic as well as multi-parameter oxidative stress assays in cells showed excellent correlation to the generation of acute neutrophilic inflammation and cytokine responses in the lungs of C57 BL/6 mice. Co(3)O(4), Ni(2)O(3), Mn(2)O(3), and CoO nanoparticles could also oxidize cytochrome c as a representative redox couple involved in redox homeostasis. While CuO and ZnO generated oxidative stress and acute pulmonary inflammation that is not predicted by E(c) levels, the adverse biological effects of these materials could be explained by their solubility, as demonstrated by ICP-MS analysis. These results demonstrate that it is possible to predict the toxicity of a large series of MOx nanoparticles in the lung premised on semiconductor properties and an integrated in vitro/in vivo hazard ranking model premised on oxidative stress. This establishes a robust platform for modeling of MOx structure-activity relationships based on band gap energy levels and particle dissolution. This predictive toxicological paradigm is also of considerable importance for regulatory decision-making about this important class of engineered nanomaterials.

Download full-text


Available from: Xiang Wang,
  • Source
    • "Cells have multiple 103 pathways to limit ROS build-up (D'Autréaux and Toledano, 2007), but loss of cellular function 104 can occur when this capacity is exhausted. As summarized in Fig. 1d and 1f, metal and metal- 105 oxide NPs can induce ROS outside the cell, at the cell membrane, and inside the cell (when NPs 106 are internalized) by direct interaction with biomolecules in the environmental medium, the 107 cell/outer membrane, and organic cytoplasmic components, respectively, or via similar 108 interactions of dissolved metal ions with biomacromolecules (Park et al., 2009; Cabiscol et al., 109 2010; Dutta et al., 2012); recent studies of metal-oxide NPs have attempted to correlate 110 conduction band-edge positioning with respect to cellular redox potential and the resulting ability 111 to generate ROS (Zhang et al., 2012; Kaweeteerawat et al., 2015). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Metal and metal oxide nanoparticles (NPs) are used in numerous applications and have high likelihood of entering engineered and natural environmental systems. Careful assessment of the interaction of these NPs with bacteria, particularly biofilm bacteria, is necessary. This perspective discusses mechanisms of NP interaction with bacteria and identifies challenges in understanding NP-biofilm interaction, considering fundamental material attributes and inherent complexities of biofilm structure. The current literature is reviewed, both for planktonic bacteria and biofilms; future challenges and complexities are identified, both in light of the literature and a dataset on the toxicity of silver NPs toward planktonic and biofilm bacteria. This perspective aims to highlight the complexities in such studies and emphasizes the needs for systematic evaluation of NP-biofilm interaction.
    Frontiers in Microbiology 06/2015; DOI:10.3389/fmicb.2015.00677/abstract · 3.99 Impact Factor
  • Source
    • "Their conclusion was in a good agreement with the results of Burello and Worth (2011b), who found that the conduction band energy of oxide NPs is related to their toxicity. Similar findings have also been reported by Zhang et al. (2012), who indicated that the oxidative stress induced by MO-NPs could be linked to their conduction and valance band energies. More recently, Singh and Gupta (2014) attempted to build classification and regression nano-(Q)SAR models using ensemble methods such as decision tree forest (DTF) and decision tree boost (DTB). "
    [Show abstract] [Hide abstract]
    ABSTRACT: There is increasing recognition that some nanomaterials may pose a risk to human health and the environment. Moreover, the industrial use of the novel engineered nanomaterials (ENMs) increases at a higher rate than data generation for hazard assessment; consequently, many of them remain untested. The large number of nanomaterials and their variants (e.g., different sizes and coatings) requiring testing and the ethical pressure towards nonanimal testing means that in a first instance, expensive animal bioassays are precluded, and the use of (quantitative) structure–activity relationships ((Q)SARs) models as an alternative source of (screening) hazard information should be explored. (Q)SAR modelling can be applied to contribute towards filling important knowledge gaps by making best use of existing data, prioritizing the physicochemical parameters driving toxicity, and providing practical solutions for the risk assessment problems caused by the diversity of ENMs. This paper covers the core components required for successful application of (Q)SAR methods to ENM toxicity prediction, summarizes the published nano-(Q)SAR studies, and outlines the challenges ahead for nano-(Q)SAR modelling. It provides a critical review of (1) the present availability of ENM characterization/toxicity data, (2) the characterization of nanostructures that meet the requirements for (Q)SAR analysis, (3) published nano-(Q)SAR studies and their limitations, (4) in silico tools for (Q)SAR screening of nanotoxicity, and (5) prospective directions for the development of nano-(Q)SAR models.
    Particuology 06/2015; 21:1-19. DOI:10.1016/j.partic.2014.12.001 · 2.11 Impact Factor
  • Source
    • "These works highlight that any nanomaterial for biomedical application use must be considered for its orientation and surface chemistry to assess the conditions which render it biocompatible. However the downstream effects of the material must also be evaluated for environmental impact if they are to be commercially exploited [18]–[22]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Group IV Nanowires have strong potential for several biomedical applications. However, to date their use remains limited because many are synthesised using heavy metal seeds and functionalised using organic ligands to make the materials water dispersible. This can result in unpredicted toxic side effects for mammalian cells cultured on the wires. Here, we describe an approach to make seedless and ligand free Germanium nanowires water dispersible using glutamic acid, a natural occurring amino acid that alleviates the environmental and health hazards associated with traditional functionalisation materials. We analysed the treated material extensively using Transmission electron microscopy (TEM), High resolution-TEM, and scanning electron microscope (SEM). Using a series of state of the art biochemical and morphological assays, together with a series of complimentary and synergistic cellular and molecular approaches, we show that the water dispersible germanium nanowires are non-toxic and are biocompatible. We monitored the behaviour of the cells growing on the treated germanium nanowires using a real time impedance based platform (xCELLigence) which revealed that the treated germanium nanowires promote cell adhesion and cell proliferation which we believe is as a result of the presence of an etched surface giving rise to a collagen like structure and an oxide layer. Furthermore this study is the first to evaluate the associated effect of Germanium nanowires on mammalian cells. Our studies highlight the potential use of water dispersible Germanium Nanowires in biological platforms that encourage anchorage-dependent cell growth.
    PLoS ONE 09/2014; 9(9):e108006. DOI:10.1371/journal.pone.0108006 · 3.23 Impact Factor
Show more