Safe Nano Design Molecule Manufacturing Market

Transcription

1 August 14 16, 212 College of Nanoscale Science & Engineering (CNSE) of the University at Albany National Institute for Occupational Safety and Health (NIOSH) Prevention through Design Program Safe Nano Design Molecule Manufacturing Market Session 1: Design of safer nano molecules Panel Discussion on Screening, Characterizing, and Detecting Nanomaterials How molecular design drives biological effects Christie Sayes, PhD Center for Aerosol and Nanomaterials Engineering RTI International

2 DISEASE-FREE CONCEPT 1: Themes in Nanotoxicology that Influence Other Fields Approach: The scale of health using the hierarchical oxidative stress model Level of Oxidative Stress Increasing DISEASED no observable adverse effects no extended adverse effects immunological response Increasing Particle Concentration Xiao GG, et al (23) Journal of Biological Chemistry 278(5): Barzilai A;, et al (24) DNA Repair 3(8-9): Sayes CM, et al (29) Systems Biology. Ed. Saura C. Sahu, Johns Wiley and Sons Ltd.

3 CONCEPT 1: Some Thoughts Many of the markers of toxicity are also pro-inflammatory mediators. This type of induced response is desirable in some cases - like a vaccine. Individual parameters may be associated with specific phenomena Caspase and oxygenase Extracellular cytoplasm leakage caused by peroxy radical formation on cellular membranes However, these acellular markers may not be indicative of the entire tissue system it is important to consider the combined response in terms of magnitude and duration of each cellular response as a signature of transition from reversible transient to irreversible toxic response. Example = glutathione (indicative of this transition from normal transient phenomenon to toxic cell response)

4 A Life-Cycle Approach: Possibly Applicable to Medicine and Consumer Products Raw Materials Production Product Manufacturing Consumer Use Product End of Life Step 1: Material Characterization of Pristine Engineered Nanomaterial Step 2: Formulate Nanocomposite or Other Nano-Enabled Material Step 3: Simulate Wear-and-Tear or Weathering Conditions Step 4: Measure Exposures Step 5: Perform Focused Toxicity Testing Step 6: Assess and Manage Risks

5 CONCEPT 2: Influence of Zeta Potential Effects of ph on a metal oxide nanoparticle Berg JM, Romoser A, Banerjee N, Zebda R, Sayes CM; (29) Nanotoxicology, 3(4):

6 Cellular viability (%) Cellular viability (%) Cellular viability (%) Zeta potential (mv) Size (nm) CONCEPT 2: Influence of Zeta Potential 8 model NP 25 6 TiO Al 2 O ph control cells ph TiO ph Al 2 O hr 24hr 48hr Exposure time 1hr 24hr 48hr Exposure time 1hr 24hr 48hr Exposure time

7 CONCEPT 2: Material Characterization & Physiologically Relevant Fluids Can we predict how nanomaterials would behave in physiological compartments? Gastric Acid Lysosomal Fluid Intestine & Urine Blood ph Level < Metal oxide nanomaterial Zeta potential (mv) / Average agglomerate size (nm) TiO 2 +46/ /186 +7/239-37/46 ZnO +5/36 +44/ /12-3/117 Al 2 O 3 +45/ / /24-4/35 CeO / /234 +2/259-6/285 Fe 2 O /18-9/174-15/17-47/83 TiO 2 and Fe 2 O 3 nanoparticles demonstrate strongly charged agglomerates at ph=7.4

8 Zeta Potential (mv) CONCEPT 2: Influence of Zeta Potential on Different Samples but Same Composition ZnO 1 ZnO 2 ZnO 3 1 nm 1 nm 1 nm ZnO 1 ZnO 2 ZnO Size (nm) ph ph ph

9 CONCEPT 2: More Thoughts Conclusions from the literature have led to the premise that there are two primary physicochemical properties of small particles, including nanoparticles, which influence their stability, mobility, and toxicity. These two primary physicochemical properties are as follows: Surface modification or conjugation to other molecules Physical contact with cells The former influences particle aggregation state, determines individual particle suspendability, and affects susceptibility to degradation. The latter affects cellular uptake mechanism substantially.

10 CONCEPT 3: Differential Cellular Uptake Mechanisms Sayes CM, Romoser A, Banerjee N; (29) The Role of Oxidative Stress in Nanotoxicology. Systems Biology. Ed. Saura C. Sahu, Johns Wiley and Sons Ltd.

11 CONCEPT 3: Can the Surface Make a Difference? Aim Determine if surface modification (in this case oxidation) has an effect on cell viability. Conclusion Co-exposure to carbon black and Fe 2 O 3 particles can cause oxidative stress that is significantly greater than the additive effects of exposures to either particle type alone. The observed oxidative stress is mitigated if the freshly prepared carbon black is oxidized before exposure to cells. Berg JM, Ho S, Hwang W, Zebda R, Cummins K, Soriaga M, Taylor R, Guo B, Sayes CM. (21) Chemical Research in Toxicology, 23(12):

12 CONCEPT 3: Conclusions Ultimately, most particles sequester in membrane-bound vesicles where the acidification process begins. The acidification process usually breaks the particle down into their ions or molecules, releasing then in a concentrated dose to specific tissues most vulnerable to particle deposition. While not all mechanisms are known within this general field of study, most agree that cellular uptake, surface charge, and propensity to dissociate into ions or molecule plays a large role in a cell s and a tissue s response to particles.