Exploring the Biotic-Abiotic Interface: Implications for Nano - PowerPoint PPT Presentation

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

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?

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

Anatomy of the bronchiolar alveolus clusters

Bronchiole Alveolar Structure Maina & van Gils (2001) Comp. Biochem and Physiol. 130(4)781-798.

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

Water: the molecule of life

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

“ 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

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

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

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

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

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

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

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

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

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

Ceria nanowires introduced shape-dependent toxicity Ceria nanowires introduced NIEHS-funded Center for Nanobiology and Predictive Toxicology shape-dependent toxicity Macrophage 300 THP-1 cells R AR 0= 1 IL-1 β 0 R IL-1 β activity (pg/mL) 250 lysosome 1 R IL-1 β NALP3 2 200 R AR 6 3 Ф = 7 nm R 150 IL-1 β 4 pro-IL-1 β 100 AR 7>200 AR7 N 50 AR 0-5 0 Inflammasome activation 0 25 50 75 100 125 L = 1~2 μ m Concentration (µg/mL) AR: aspect ratio SEM TEM AR7 AR7 THP-1 cells THP-1 cells Frustrated endocytosis Lysosomal Damage

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?

Attribution: CP Weis

Nano-sized mineral fibrils from Western Montana Attribution:

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

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

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):269- 273 .

Size – based Risk Management: a good idea? “ Fibres shorter than 5 m m 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 m m in length, were highly statistically significant predictors of lung cancer or asbestosis mortality. ” Stayner et al. (2008) Occ. Env. Med 65(9):613

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.