Custom-designed nanomaterial libraries for testing metal oxide toxicity

Abstract

Advances in aerosol technology over the past 10 years have enabled the generation and design of ultrafine nanoscale materials for many applications. A key new method is flame spray pyrolysis (FSP), which produces particles by pyrolyzing a precursor solution in the gas phase. FSP is a highly versatile technique for fast, single-step, scalable synthesis of nanoscale materials. New innovations in particle synthesis using FSP technology, including variations in precursor chemistry, have enabled flexible, dry synthesis of loosely agglomerated, highly crystalline ultrafine powders (porosity ≥ 90%) of binary, ternary, and mixed-binary-and-ternary oxides. FSP can fulfill much of the increasing demand, especially in biological applications, for particles with specific material composition, high purity, and high crystallinity. In this Account, we describe a strategy for creating nanoparticle libraries (pure or Fedoped ZnO or TiO₂) utilizing FSP and using these libraries to test hypotheses related to the particles' toxicity. Our innovation lies in the overall integration of the knowledge we have developed in the last 5 years in (1) synthesizing nanomaterials to address specific hypotheses, (2) demonstrating the electronic properties that cause the material toxicity, (3) understanding the reaction mechanisms causing the toxicity, and (4) extracting from in vitro testing and in vivo testing in terrestrial and marine organisms the essential properties of safe nanomaterials. On the basis of this acquired knowledge, we further describe how the dissolved metal ion from these materials (Zn²⁺ in this Account) can effectively bind with different cell constituents, causing toxicity. We use Fe-S protein clusters as an example of the complex chemical reactions taking place after free metal ions migrate into the cells. As a second example, TiO₂ is an active material in the UV range that exhibits photocatalytic behavior. The induction of electron-hole (e⁻/h⁺) pairs followed by free radical production is a key mechanism for biological injury. We show that decreasing the bandgap energy increases the phototoxicity in the presence of near-visible light. We present in detail the mechanism of electron transfer in biotic and abiotic systems during light exposure. Through this example we show that FSP is a versatile technique for efficiently designing a homologous library, meaning a library based on a parent oxide doped with different amounts of dopant, and investigating the properties of the resulting compounds. Finally, we describe the future outlook and state-of-the-art of an innovative two-flame system. A double-flame reactor enables independent control over each flame, the nozzle distances and the flame angles for efficient mixing of the particle streams. In addition, it allows for different flame compositions, flame sizes, and multicomponent mixing (a grain-grain heterojunction) during the reaction process.

Figure 1

Physicochemical characterization of undoped and Fe doped ZnO NPs. [(a),(b)] Matching crystal structure with HRTEM image for undoped and Fe doped ZnO. No detectable structural deviation observed [(c),(d)] d-orbitals splitting of Zn²⁺ and Fe²⁺ [(e)–(g)] Induction of OH-1 expression and Jun kinase activation by immuno-blotting and TNF-activation of ZnO, CeO₂ or TiO₂ (h)–(j) Time dependent toxicity evaluation. Animals were euthanized and BAL fluid was collected to determine PMN numbers, LDH, and albumin levels (supplementary section).^,

Figure 2

(a) Dissolution kinetics of pure or Fe doped ZnO NPs (b) Toxicity evaluation for ZnO, CeO₂ or TiO₂ with florescent dyes (c) toxicity reduction with increase in Fe content in ZnO (safe-by-design strategy).

Figure 3

The Fe-S cluster degradation and respective charge transfer during the cellular Fe-S cluster metabolism through ZnO exposure and rectification of the protein with subsequent Fe addition through doped ZnO NPs. The channels in the cell membranes enhance the ions to migrate inside the cell for complex reactions as shown in the figure.

Figure 4

Near-visible light induced ROS and evidence of the oxidative stress (a) near-visible light irradiation of TiO₂ or Fe doped TiO₂ NPs in the cell, (b) ROS causing NATA degradation in the cell, (c) High throughput screening (HTS) used to determine cell death accompanied by various oxidative stress pathways, (d) oxidative stress scavenger (NAC) for demonstrating the reduction of the phototoxicity.

Figure 5

The versatile two reactor systems and the flame symmetry of flame spray pyrolysis for designing next generation nanoscale materials.