The goal of this program is to systematically explore the influence of physicochemical properties of size, composition, surface lability as well as charge, density, and activity of engineered nanomaterials (ENMs). The goal of this project is to define the effect of these physical/chemical properties on how ENMs interact with the intact organism, including specific target organs and specific cell types within the target organs. We will focus one ofthe major classes of ENMs, the high aspect ratio nanomaterials (HARNMs), including single wall carbon nanotubes (SWNTs) and nanowires (NWs) of various lengths. The importance of size (diameter and length) and coatings (silica as one example) to affect toxicity, retention and translocation will be assessed. HARNM with differing physical/chemical property described above will be employed in a series of systematic examinations of absorption and distribution following inhalation/ingestion experiments. Primary and secondary target organ responses will be monitored, and the influence of HARNM exposure In a model of allergy will be assessed. The overall hypothesis Is that differences in composition, size, diameter and surface coating of HARNMs will modulate the in vivo uptake, distribution and biologic effects of HARNMs in a rat model. This hypothesis will be addressed in four specific aims that will determine the effect of HARNM on 1) deposition, retention and distribution to various organs;2) respiratory system cytotoxicity, inflammation and airway remodeling;3) oxidative stress in the respiratory system;and 4) exacerbation of ainway hyperresposiveness in a sensitive model. We will address these aims using a transdisciplinary approach that combines inhalation toxicology, chemistry, histopathology, high resolution imaging and novel methodologies developed at UC Davis that uniquely position us to successfully address the biological effects of these materials. The long term goal is to identify features of these materials that reduce their toxicity and biological effects.
; To develop and evaluate techniques and approaches to assess the potential disease burden associated with exposures to ENMs. The goal of Project 2 is to define exposure effects of high aspect ratio nanomaterials (single walled carbon nanotubes and nanowires) in an in vivo inhalation model that includes airways hyperresonsiveness.
|Holland, Nathan A; Thompson, Leslie C; Vidanapathirana, Achini K et al. (2016) Impact of pulmonary exposure to gold core silver nanoparticles of different size and capping agents on cardiovascular injury. Part Fibre Toxicol 13:48|
|Silva, Rona M; Anderson, Donald S; Peake, Janice et al. (2016) Aerosolized Silver Nanoparticles in the Rat Lung and Pulmonary Responses over Time. Toxicol Pathol 44:673-86|
|Patchin, Esther Shin; Anderson, Donald S; Silva, Rona M et al. (2016) Size-Dependent Deposition, Translocation, and Microglial Activation of Inhaled Silver Nanoparticles in the Rodent Nose and Brain. Environ Health Perspect 124:1870-1875|
|Das, Gautom K; Anderson, Donald S; Wallis, Chris D et al. (2016) Novel multi-functional europium-doped gadolinium oxide nanoparticle aerosols facilitate the study of deposition in the developing rat lung. Nanoscale 8:11518-30|
|Anderson, Donald S; Patchin, Esther S; Silva, Rona M et al. (2015) Influence of particle size on persistence and clearance of aerosolized silver nanoparticles in the rat lung. Toxicol Sci 144:366-81|
|Anderson, Donald S; Silva, Rona M; Lee, Danielle et al. (2015) Persistence of silver nanoparticles in the rat lung: Influence of dose, size, and chemical composition. Nanotoxicology 9:591-602|
|Liu, Ying X; Karsai, Arpad; Anderson, Donald S et al. (2015) Single-Cell Mechanics Provides an Effective Means To Probe in Vivo Interactions between Alveolar Macrophages and Silver Nanoparticles. J Phys Chem B 119:15118-29|
|Silva, Rona M; Anderson, Donald S; Franzi, Lisa M et al. (2015) Pulmonary effects of silver nanoparticle size, coating, and dose over time upon intratracheal instillation. Toxicol Sci 144:151-62|
|Li, Xueting; Xue, Min; Raabe, Otto G et al. (2015) Aerosol droplet delivery of mesoporous silica nanoparticles: A strategy for respiratory-based therapeutics. Nanomedicine 11:1377-85|
|Holland, N A; Becak, D P; Shannahan, Jonathan H et al. (2015) Cardiac Ischemia Reperfusion Injury Following Instillation of 20 nm Citrate-capped Nanosilver. J Nanomed Nanotechnol 6:|
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