Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity

Transcription

1 Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National Capitol Area Chapter Society of Toxicology Christopher P. Weis, Ph.D., DABT. National Institutes of Environmental health Science

2 Objectives What s going on at the Biotic Abiotic interface? Why is the Biotic-Abiotic interface important? What are the implications for Health Risks and Regulations?

3 Basic Respiratory Anatomy Images developed under contract to the National Institutes of Health

4 Anatomy of the bronchiolar alveolus clusters

5 Bronchiole Alveolar Structure Maina & van Gils (2001) Comp. Biochem and Physiol. 130(4)

6 Gas exchange in the lung The alveolarcapillary membrane is just 0.2 microns thick! Blood volume in capillary space Is about 70 ml. Blood flow through the lung is about 5L/min.

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8 Water: the molecule of life

9 Solid Liquid Interface Nel et al. (2009) Nat. Mater. 8:543

10 C60 molecule can readily jump into the bilayer and translocate the membrane within a few milliseconds Qiao, R. et al. (2007) Nano Lett. 7(3):614

11 Small chemical modifications Can have big Consequences The simulation results indicate that, although a pristine C60 molecule can readily jump into the bilayer and translocate the membrane within a few milliseconds, the C60(OH)20 molecule can barely penetrate the bilayer. Qiao, R. et al. (2007) Nano Lett. 7(3):614

12 ENM Biomolecule Interactions Nel et al. (2009) Nat. Mater. 8:543

13 Nanoparticle endocytosis at the cell membrane: The clathrin-coated vessicle Nel et al. (2009) Nat. Mater. 8:543

14 Clathrin coated vessicles transporting materials across the cell membrane Attribution: University of British Columbia Dept. of Zoology (Permission requested)

15 Objectives What s going on at the Biotic Abiotic interface? Why is the Biotic-Abiotic interface important? What are the implications for OELs?

16 Coronavirus (~70-200nm) Coronavirus on a Mouse epithelial cell ~40,000X mag. Attribution: F.A. Murphy, Univ.Texas Medical Branch

17 Corona Virus on Cultured Cell Attribution: Dr. Steve Patterson Surface

18 Targeted Docetaxel Nanoparticle Hrkach et al. (2012) Sci. Trans. Med 4:128ra39 Docetaxel MW=807 Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile. ~90 nm

19 Strain-specific differential response to TOPO-PMAT Cd- Se/ZnS QDs Univ. Washington Nanotoxicology Center Oropharyngeal aspiration 10 nm solution, 8 h PE BALF Neutrophils Mouse Strains

20 THP-1 cells THP-1 cells IL-1β activity (pg/ml) Ceria nanowires introduced shape-dependent Ceria nanowires introduced toxicity NIEHS-funded Center for Nanobiology shape-dependent and Predictive Toxicology toxicity Macrophage AR 0= 1 lysosome NALP3 IL-1β pro-il-1β IL-1β N Inflammasome activation SEM AR7 Ф = 7 nm AR 7>200 L = 1~2 μm AR: aspect ratio AR7 THP-1 cells AR 6 AR7 AR Concentration (µg/ml) TEM IL-1β R 0 R 1 R 2 R 3 R 4 Frustrated endocytosis Lysosomal Damage

21 Objectives What s going on at the Biotic Abiotic interface? Why is the Biotic-Abiotic interface important? What are the implications for Risks and Regulations?

22 Attribution: CP Weis

23 Attribution: Nano-sized mineral fibrils from Western Montana

24 Phagocytosis of asbestos fibers pulmonary alveolar macrophage cell attempting to engulf and ingest several long mineral fibers incomplete ingestion of bio-persistent fibers can lead to extensive selective release of proteolytic enzymes and ROS from the frustrated PAMs

25 Microscopic and macroscopic lung abnormalities caused by durable fibers Radiograph of Pleural plaques mineral bodies ferruginous bodies Anatomy of Pleural plaques Attribution: Med. Digital Library. Univ. of Michigan

26 High Resolution Computed Tomography (HRCT) of a pleural plaque HRCT scan of a 45 Y.O. female with secondary (take home) exposure to nano particle taconite dust in the Upper Peninsula of Michigan. Harbut et al. (2009) Int J Occup Environ Health 15(3):

27 Size based Risk Management: a good idea? Fibres shorter than 5 mm have traditionally not been counted by methods used for regulatory standards for asbestos because these methods were developed to provide a reproducible index of fibre exposure. The findings from our analysis show that cumulative exposures to all fibre size indices, including fibres <5 mm in length, were highly statistically significant predictors of lung cancer or asbestosis mortality. Stayner et al. (2008) Occ. Env. Med 65(9):613

28 Summary Biophysical chemistry at the abiotic-biotic interface is critical to understanding toxicity of engineered nanomaterials; Characterization of nanomaterials (especially effects on the A-B interface) is key; Toxicity studies for nanomaterials must include minimal physico-chemical characterization.