Tying Distinct Nanoparticle Properties to Cellular Interactions, Fate and Respons

将独特的纳米颗粒特性与细胞相互作用、命运和反应联系起来

• 批准号: 8077706
• 负责人: Galya Orr
• 金额: $ 8.48万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8077706
• 关键词: Address; Adverse effects; Air; Alveolar; Alveolar Cell; Alveolar Macrophages; Apoptosis; Artificial nanoparticles; Breathing; Cell physiology; Cells; Chemicals; Deposition; Electron Microscopy; Engineering; Ensure; Environment; Environmental Health; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Evaluation; Exclusion; Exposure to; Fluorescence; Fluorescence Microscopy; Gene Proteins; Goals; Guidelines; Health; Human; Imaging Techniques; Individual; Inflammatory; Inflammatory Response; Liquid substance; Mass Spectrum Analysis; Medical; Membrane; Methods; Molecular Biology; Molecular Biology Techniques; Morphology; Occupational Exposure; Organelles; Oxidative Stress; Pathway interactions; Pharmaceutical Preparations; Phase; Physical Chemistry; Property; Public Health; Research; Research Personnel; Resolution; Respiratory System; Respiratory tract structure; Reverse Transcriptase Polymerase Chain Reaction; Safety; Science; Silicon Dioxide; Source; Structure; Surface; Synchrotrons; Techniques; Time; Titania; Toxic effect; base; biomaterial compatibility; chemical property; design; experience; fluorescence imaging; in vivo; nanomaterials; nanoparticle; nanoscale; particle; physical property; planetary Atmosphere; protein expression; public health relevance; response; single molecule; trafficking

DESCRIPTION (provided by applicant): This application is submitted in response to Grand Opportunities (RC2): Engineered Nanomaterial Environmental Health and Safety. The increasing use of engineered nanomaterials in industrial and medical applications is expected to increase both unintended environmental or occupational exposures and intended medical or direct consumer exposures, but the impact of such exposures on human health is unclear. The potential toxicity or biocompatibility of engineered nanomaterials is governed by the cellular interactions and fate of the particles, which dictate the cellular response and ultimately determine the impact on human health. The cellular interactions and subsequent response of the cells are governed by the physical and chemical properties of the particles, but the relationships between particle properties and these cellular processes are far from being understood. Furthermore, the properties of nanomaterials are likely to be modified by the environment, such as ambient air, but these changes are also unclear. The purpose of this proposal is to identify relationships between distinct properties of airborne engineered nanomaterials and their cellular interactions, fate, and response in alveolar epithelial cells at the air- liquid interface with the goal of supporting predictive evaluation of inhaled nonmaterial's toxicity or biocompatibility. Airborne nanomaterials that enter the respiratory tract are likely to be deposited in the alveolar region, where alveolar epithelial cells are found. These cells provide a vulnerable target for particles that escape the first line of defense by the alveolar macrophages. Accumulating observations indicate that nanomaterials are likely to be presented to alveolar cells in vivo as individual particles or small nanoscale aggregates, which differ from the larger particles in their ability to interact with the cells. We will establish methods for realistic exposures to well-defined monodispersed nanomaterials in ambient air for delineating relationships between distinct properties that are relevant to airborne particles and their impact on alveolar epithelial cells at the air- liquid interface. Size exclusion methods will ensure exposures to individual nanoparticles or small nanoscale aggregates, as they are likely to be presented to the cells in vivo. Building on our experience in quantitative fluorescence imaging with single molecule sensitivity, combined with molecular biology techniques, we will investigate the cellular interactions and fate of one nanoparticle or nanoscale aggregate at a time, delineating cellular processes that are relevant to the properties of the individual nanoparticle and the exposures in vivo. We propose to focus on surface modified and unmodified titania and amorphous silica nanoparticles, which have been widely used in diverse applications and pose a significant source for potential airborne exposures. Using analytical and physical chemistry methods, the properties of the particles, collected at the air-liquid interface, will be characterized. This information will derive changes that occur to nanomaterials in ambient air and delineate properties that are relevant to airborne nanoparticles and their cellular interactions and impact in vivo. Together, our studies will gain critical new relationships between properties of airborne nanomaterials and their cellular interactions, fate and response, supporting predictive evaluation of toxicity or biocompatibility of inhaled nanomaterials. The new information will have a large scale impact by guiding preventative approaches that will protect human health from adverse effects of engineered nanomaterials and the design of safe nanomaterials for new industrial and medical applications. PUBLIC HEALTH RELEVANCE: The increasing use of engineered nanomaterials in industrial and medical applications is expected to increase both unintended environmental or occupational exposures and intended medical or direct consumer exposures, but the impact of such exposures on human health is unclear. The potential toxicity or biocompatibility of engineered nanomaterials is governed by the cellular interactions and fate of the particles, which dictate the cellular response and ultimately determine the impact on human health. These cellular interactions and subsequent response of the cells are governed by the physical and chemical properties of the particles, but the relationships between particle properties and these cellular processes are far from being understood. Our research will address the specific call and public health needs by identifying critical new relationships between properties of airborne nanomaterials and their cellular interactions, fate and response, supporting predictive evaluation of toxicity or biocompatibility of inhaled nanomaterials. The new information will have a large scale impact by guiding preventative approaches that will protect human health from adverse effects of engineered nanomaterials and the design of safe nanomaterials for new industrial and medical applications.

描述（由申请人提供）：此申请是针对大机会（RC2）提交的：工程纳米材料的环境健康与安全。在工业和医疗应用中，工程纳米材料的使用越来越多，预计将增加意外的环境或职业暴露以及预期的医疗或直接消费者暴露，但这种暴露对人类健康的影响尚不清楚。工程纳米材料的潜在毒性或生物相容性受颗粒的细胞相互作用和命运的控制，这决定了细胞反应，并最终决定了对人类健康的影响。细胞相互作用和随后的细胞反应受颗粒的物理和化学特性的控制，但是粒子特性与这些细胞过程之间的关系远非被理解。此外，纳米材料的特性可能会被环境（例如环境空气）修改，但这些变化也不清楚。该提案的目的是确定空气中工程纳米材料的不同特性与空气液体界面肺泡上皮细胞中的细胞相互作用，命运和反应之间的关系，目的是支持对非材料非物质毒性或生物相容性的预测评估。进入呼吸道的空气传播纳米材料可能会沉积在发现肺泡上皮细胞的肺泡区域。这些细胞为避开肺泡巨噬细胞的第一道防线提供了脆弱的靶标。积累的观察结果表明，纳米材料可能以单个颗粒或小纳米级聚集体为肺泡细胞，与较大的颗粒与细胞相互作用的能力不同。我们将建立对环境空气中定义明确的单分散纳米材料的现实暴露的方法，以划定与空气颗粒相关的不同性质之间的关系及其对空气液体界面上肺泡上皮细胞的影响。大小排除方法将确保暴露于单个纳米颗粒或小纳米级骨料，因为它们可能会在体内呈现给细胞。基于我们以单分子敏感性的定量荧光成像的经验，结合了分子生物学技术，我们将一次研究一种纳米粒子或纳米级聚集的细胞相互作用和命运，并划定与单个纳米属物质和exposures and exposures in vivo的特性相关的细胞过程。我们建议专注于表面修饰和未修饰的二二氧化钛和无定形二氧化硅纳米颗粒，它们已广泛用于不同的应用中，并为潜在的空降暴露提供了重要的来源。使用分析和物理化学方法，将表征在空气界面上收集的颗粒的性能。这些信息将得出与空气中的纳米颗粒及其细胞相互作用相关的环境空气中纳米材料发生的变化，并影响体内。总之，我们的研究将获得空气纳米材料的特性与其细胞相互作用，命运和反应之间的关键关系，并支持对吸入纳米材料的毒性或生物相容性的预测评估。新信息将通过指导预防方法产生大规模影响，该方法将保护人类健康免受工程纳米材料的不利影响，并针对新的工业和医疗应用设计安全的纳米材料。 公共卫生相关性：预计工业和医疗应用中工程纳米材料的使用越来越多，将增加意外的环境或职业暴露以及预期的医疗或直接消费者暴露，但是这种暴露对人类健康的影响尚不清楚。工程纳米材料的潜在毒性或生物相容性受颗粒的细胞相互作用和命运的控制，这决定了细胞反应，并最终决定了对人类健康的影响。这些细胞相互作用和随后的细胞反应受颗粒的物理和化学特性的控制，但是粒子特性与这些细胞过程之间的关系远非被理解。我们的研究将通过确定机载纳米材料及其细胞相互作用，命运和反应之间的关键新关系来解决特定的呼叫和公共卫生需求，从而支持对吸入纳米材料的毒性或生物相容性的预测评估。新信息将通过指导预防方法产生大规模影响，该方法将保护人类健康免受工程纳米材料的不利影响，并针对新的工业和医疗应用设计安全的纳米材料。

项目成果

Facile method to stain the bacterial cell surface for super-resolution fluorescence microscopy.

• DOI: 10.1039/c4an00574k
• 发表时间: 2014-06-21
• 期刊: The Analyst
• 作者: Gunsolus IL;Hu D;Mihai C;Lohse SE;Lee CS;Torelli MD;Hamers RJ;Murhpy CJ;Orr G;Haynes CL
• 通讯作者: Haynes CL

Intracellular accumulation dynamics and fate of zinc ions in alveolar epithelial cells exposed to airborne ZnO nanoparticles at the air-liquid interface.

• DOI: 10.3109/17435390.2013.859319
• 发表时间: 2015-02
• 期刊: Nanotoxicology
• 影响因子: 5
• 作者: Mihai C;Chrisler WB;Xie Y;Hu D;Szymanski CJ;Tolic A;Klein JA;Smith JN;Tarasevich BJ;Orr G
• 通讯作者: Orr G

Cells Respond to Distinct Nanoparticle Properties with Multiple Strategies As Revealed by Single-Cell RNA-Seq.

• DOI: 10.1021/acsnano.6b05452
• 发表时间: 2016-10
• 期刊: ACS nano
• 影响因子: 17.1
• 作者: H. Mitchell;L. M. Markillie;W. Chrisler;Matthew J. Gaffrey;Dehong Hu;C. Szymanski;Yumei Xie;Eric S. Melby;A. Dohnalkova;Ronald C. Taylor;Eva K Grate;S. Cooley;J. Mcdermott;A. Heredia-Langner;G. Orr