Nanomaterials for Studies Across the CEIN Jeffrey I. Zink and Zhaoxia (Ivy) Ji Theme 1 and Core B

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1 Nanomaterials for Studies Across the CEIN Jeffrey I. Zink and Zhaoxia (Ivy) Ji Theme 1 and Core B y participants: C. Jeffrey Brinker, Mark Hersam, Lutz Mädler and Galen S Part 1: Introduction to fundamental projects 1. Relationships between utcomes 2. Relationships between utcomes 3. Relationships between Biological utcomes 4. Relationships between utcomes ENM Electronic Structure and Biological ENM Shape/ze and Biological ENM Surface Structure/Chemistry and Novel ENM Properties and Environmental Part 2: Examples of recent results 5. Dissolution properties

2 Relationships between ENM Electronic Structure and Biological utcomes Prior studies have demonstrated that there is a good correlation between the conduction band energy of wide band gap metal oxide semiconductor nanoparticles and adverse biological responses. The correlation was attributed to electron transfer from redox-active biomolecules to the nanoparticles. The observed correlations were good but not perfect.

3 Use of Metal xide Nanoparticle Band Gap To Develop a Predictive Paradigm for xidative Stress and Acute Pulmonary Inflammation H. Zhang1, Z. Ji1, T. Xia1,2, H. Meng2, C. Low-Kam3, R. Liu1,4, S. Lin1, X. Wang1, Y. Liao2, M. Wang2, L. Li1, R. Damoiseaux1,5, D. Telesca3, Y. Cohen1,4, J. I. Zink1,6, A. E. Nel1,2 1California NanoSystems Institute, 2Division of NanoMedicine, 3Department of Biostatistics, 4 Department of Chemical & Biomolecular Engineering, 5 Molecular Shared Screening Resources, 6Department of Chemistry & Biochemistry, UCLA We demonstrated for 24 metal oxide 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 (Ec) levels with the cellular redox potential (-4.12 to ev) is strongly correlated to the ability of Co34, Cr23, Ni23, Mn23, and Co nanoparticles to induce oxygen radicals, oxidative stress, and inflammation. While Cu and Zn generated oxidative stress and acute pulmonary inflammation that is not predicted by Ec levels, the adverse biological effects of these materials was explained by their solubility. H. Zhang, Z. Ji, and J.I. Zink, and A.E. Nel et al. ACS Nano 6, , 2012.

4 Current and Proposed Studies Tune band energies using libraries of mixed metal oxides, p and n doping of metal oxides, p-n junctions between different metal oxides Compare catalytic activities of metal oxide nanoparticles with biological outcomes Use novel syntheses including 2-flame spray pyrolysis and ink-jet multi-metal methodology to develop libraries for high-throughput screening Study interactions of two dissimilar materials ranging from intimate contact (p-n junctions in individual semiconductor particles) to non-covalent interactions between nanoparticles

5 Relationships between ENM Shape/ze and Biological utcomes Nano-rods and nano-wires with large aspect ratios have been shown to cause inflammatory responses and cell death even when nanospheres of the same chemical compositions are nontoxic. Libraries of metal oxides nanorods and wires and of carbon nanotubes will be prepared and biological responses to these materials will be measured. Commercial nanoparticles (for example silver and ceria) often contain non-spherical particles; studies will be carried out to determine if there is a critical aspect ratio or length beyond which adverse biological outcomes are initiated. Controlled aggregation of nanospheres into a

6 Relationships between ENM Surface Structure/Chemistry and Biological utcomes Surface derivatization is a critical factor in influencing cell-nanoparticle interactions. Many synthetic preparations require surface coatings, many commercial nanoparticles are suface-coated, and most nanoparticles acquire coatings of biomolecules in both tissue culture and aqueous media in the environment. The prior history of nanoparticles including the temperature at which they were synthesized, calcined or annealed affect their effects on cells. Fumed silica synthesized at high temperature is toxic whereas silica synthesized at low temperatures is not.

7 Proposed and Current Studies Libraries of metal oxide nanoparticles made by flame-spray pyrolysis (high temperature), hydrothermal methods (moderate temperatures) and sol-gel or aerosol methods (low temperature) will be synthesized. Safe by design nanomaterials may be synthesizable by changing the synthesis temperature. Carbon nanotubes will be coated with a variety of polymers for high-throughput screening. Metal oxide nanoparticles will be deliberately coated with cationic, anionic and neutral molecules to determine their effect on toxicity. Metal and metal oxide coatings ranging from one to several atoms thick will be applied using

8 Relationships between Novel ENM Properties and Environmental utcomes The largest group of nanomaterials that will be studied in this project are layered materials such as clays and certain metal oxides (LiCo2) and chalcogenides (MoS2). The former are ubiquitous natural (geological) materials and the latter are in use in batteries and solar energy conversion. These materials can exfoliate (strip off layers) to expose new surfaces, or can intercalate ions (such as Li+) that change their charge and electrochemical properties. Magnetism will be useful for tracing, collecting and recovering nanoparticles from microcosims, mesocosms and the environment. Metal oxide nanoparticles of interest will be synthesized around a superparamagnetic or ferromagnetic core. The exterior of these particles

9 Promoting Collaborative Synergism Multiple P.I.s will contribute to each project (instead of each P.I. having individual projects) Electronic Structure Mädler, Stucky, Zink ENM Shape/ze Brinker, Hersam, Zink ENM Surface Structure and Chemistry Brinker, Hersam, Mädler, Zink Novel ENM Properties Brinker, Hersam, Mädler, Zink Unexpected synergy: materials for electronic structure studies and for shape studies are being synthesized by both pyrolysis and and low temperature methods. These materials may thus have different surface properties and will be useful for the studies involving surfaces

10 Nanomaterials for Studies Across the CEIN Jeffrey I. Zink and Zhaoxia (Ivy) Ji Theme 1 and Core B Part 1: Introduction to fundamental projects 1. Relationships between utcomes 2. Relationships between utcomes 3. Relationships between Biological utcomes 4. Relationships between utcomes ENM Electronic Structure and Biological ENM Shape/ze and Biological ENM Surface Structure/Chemistry and Novel ENM Properties and Environmental Part 2: Examples of recent results 5. Dissolution properties

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12 Designed Synthesis of Ce2 Nanorods and Nanowires for Studying Toxicological Effects of High Aspect Ratio Nanomaterials Z. Ji1, X. Wang1, H. Zhang1, S. Lin1, H. Meng2, B. Sun2, T. Xia1,2, A.E. Nel1,2, and J.I. Zink1,3 1California NanoSystems Institute, 2Division of NanoMedicine, 3Department of Chemistry & Biochemistry, UCLA Cerium dioxide nanorods and nanowires with aspect ratios finely tuned from 1 to >200 were synthesized using a hydrothermal method. The successful creation of a combinatorial library has made it possible, for the first time, to systematically study the role of length and aspect ratio on biological outcomes. In vitro toxicity studies showed that at lengths 200 nm and aspect ratios 22, ceria nanorods induced progressive pro-inflammatory responses and cytotoxicity. The critical aspect ratio of 22 identified here is much smaller than that in the current length-dependent theory, and is probably associated with the small diameters of these Ce2 nanowires. ur results suggest that both length and diameter components of aspect ratio should be considered when addressing the cytotoxic effects of high aspect ratio materials. S0 S2 Z. Ji, X. Wang, and A.E. Nel, and J.I. Zink et al. ACS Nano 6, , S7 S4 NSF: DBI S0 S2 S4 S7

13 Processing Pathway Dependence of Amorphous lica Nanoparticle Toxicity: Colloidal vs Pyrolytic H. Zhang1, D.R. Dunphy4, X. Jiang4, H. Meng2, B. Sun2, D. Tarn3, M. Xue3, X. Wang1, S. Lin1, Z. Ji1, R. Li2, F.L. Garcia4, J. Yang5, M.L. Kirk5, T. Xia1,2, J.I. Zink1,3, A.E. Nel1,2, C.J.. Brinker4,5,6 1California NanoSystems Institute, 2Division of NanoMedicine, 3Department of Chemistry & Biochemistry, UCLA; 4Department of Chemical and Nuclear Engineering, 5Department of Chemistry and Chemical Biology, 6Department of Molecular Genetics and Microbiology, University of New Mexico A silica library of different silica compositions was constructed to study crystallinity and surface chem-istry effects. Through physico-chemical analyses, we have determined the state of aggregation, hydroxyl concentration, relative proportion of strained and unstrained siloxane rings, and potential to generate hydroxyl radicals for each silica. Toxicity studies show that fumed silica is the most toxic of all of the silicas, and reveal a positive correlation of toxicity with hydroxyl concentration and its potential to generate RS. H. Zhang, D.R. Dunphy, A.E. Nel, C.J.. Brinker, J.I. Zink et al. NSF: DBI

14 lica Surface Chemistry loxane group Amorphous Strained ring Fumed lanol, loxane, Crystallin Surface e Reconstructi on lanol group <130o 137o Four-membered ring 144o Two-membered ring Mesoporous Unstrained ring Three-membered ring 148o Five-membered ring

15 Hydration-State Dependence of Fumed lica Toxicity Heating at high temperatures (600, 800 C) reduced the toxicity of fumed silica Toxicity of the heat-treated fumed silica reemerged upon rehydration 120 As-received 5.0 Calcined at 800 oc % Cell viability 100 Rehydrated *# *# * *# 50 # *# *# 200 Dose (µg/ml) IL-1β (x103 pg/ml) Calcined at 600 oc As-received Calcined at 600 oc Calcined at 800 oc * ## * Rehydrated * * # * # # * # Dose (µg/ml) Zhang H, Dunphy DR, Jiang X, Meng H, Sun B, Tarn D, Xue M, Wang X, Lin S, Ji Z, Li R, Garcia FL, Yang J, Kirk ML, Xia T, Zink JI, Nel A, Brinker CJ. J Am

16 Prediction of 24 Mx Toxicity Based on Conduction Band Energy u n l2 Y2 a d b Hf Zr n2 Ni b Ce Zn n Ti i2 Co r o S C C M Fe Fe C W A I L G Y N S -2 E to Vacuum (ev) H2/H + -6 H2/ Conduction band energy was proposed to correlate with toxicity Band energies of 24 Mx were measured and quantified Prediction was correct in 21 cases; incorrect prediction partly explained by dissolution -12 Zhang H, Ji Z, Xia T, Meng H, Low-Kam C, Liu R, Pokhrel S, Lin S, Wang X, Liao YP, Wang M, Li L, Rallo R, Damoiseaux R, Telesca D, Madler L, Cohen Y, Zink JI,

17 Tuning Fermi Energy Levels of Co34 by Doping 10%Fe-Co34 Co34 10%Cr-Co34 10%Cu-Co34 Normalized counts Co34 Cu-Co34 Fe-Co34 Cr-Co UPS Energy (ev) x-intercept: EF-Ev