Cytoxic and Genotoxic Effects of Manufactured Nanoparticles on Stem Cells

描述（由申请人提供）：纳米技术在生物医学应用中具有巨大潜力，并且正在研究用于诊断（例如，成像，传感器）和治疗（例如，植入物、装置、药物递送）。然而，必须首先满足一个主要的挑战：了解和量化纳米颗粒特性和生理反应之间的关系。纳米颗粒的组成、形状、电荷、表面化学和粒径如何与材料整合到活生物体中，特别是与敏感的细胞系统-干细胞的整合有关，在很大程度上是未知的。干细胞是具有自我更新和分化能力的独特细胞群。成体干细胞在我们体内不断提供新的细胞谱系。近年来，越来越多的证据表明干细胞可能是导致肿瘤发生和维持肿瘤生长的突变细胞的来源。我们前期的研究表明，碳纳米管和纳米银颗粒可以诱导小鼠胚胎干细胞的DNA损伤反应。在这项提案中，将制造四种类型的纳米颗粒（碳、银、二氧化钛和氧化锌），并评估对干细胞的毒性。这项研究将帮助我们更好地了解纳米颗粒对干细胞命运的影响，并开发评估纳米颗粒健康和安全性的方法，大大增强消费者的信心。此外，这项研究将加强研究生和本科生在代顿大学的研究。 公共卫生相关性：纳米技术革命有可能超过工业革命，并超过1万亿美元。需要确定制造的纳米颗粒的毒性及其对人类健康和环境的影响，特别是对干细胞的影响。干细胞具有无限分裂的能力，并且可以产生许多不同的细胞谱系。干细胞的功能和特性与体细胞有很大的不同。干细胞的突变可能导致癌症，并可能损害多个细胞谱系，影响后代的健康。该项目的目的是了解纳米颗粒对干细胞命运的影响，并开发一种快速且具有成本效益的方案，用于确定制造的纳米颗粒对干细胞的毒性。该提案将提供一个关于制造的纳米颗粒对干细胞毒性的全面数据库，并大大增强消费者的信心。

DESCRIPTION (provided by applicant): Nanotechnology has enormous potential for biomedical applications and is being investigated for diagnostics (e.g., imaging, sensors) and therapeutics (e.g., implants, devices, drug delivery). However, a major challenge must first be met: to understand and quantify the relationship between nanoparticle characteristics and physiological responses. How nanoparticles composition, shape, charge, surface chemistry, and particle size relate to the integration of a material into a living organism, especially to sensitive cell system-stem cells, is largely unknown. Stem cells are a unique cell population with the ability to undergo both self-renewal and differentiation. Adult stem cells constantly provide new cell lineages in our body. Recently increasing amount of evidence suggest that stem cells may be the sources of mutant cells that give rise to cancerous tumors and maintain tumor growth. Our previous studies indicated the carbon nanotube and nanosilver particles can induce a DNA damage response in mouse embryonic stem cells. In this proposal, four types of nanoparticles (carbon, silver, titanium dioxide, and zinc oxide) will be manufactured and the toxicity to stem cells will be assessed. The study will help us better understand the impact of nanoparticles to stem cell fate and develop the methods to evaluate the health and safety of nanoparticles and greatly enhance consumer confidence. In addition, this research will enhance the research for graduate and undergraduate students at the University of Dayton. PUBLIC HEALTH RELEVANCE: The nanotechnology revolution has the potential to top the industrial revolution and turn over $1 trillion. There is a need to determine the toxicity of manufactured nanoparticles and their impact on human health and the environment, especially to stem cells. Stem cells have the ability to divide indefinitely, and can give rise to many different cell lineages. The functions and properties of stem cells are very different from that of somatic cells. Mutation in stem cells can give rise to cancer and potentially compromise multiple cells lineages and affect the well being of subsequent generations. The objective of this project is to understand the impact of the nanoparticles to stem cell fate and to develop a rapid and cost effective protocol for determination of the toxicity of manufactured nanoparticles to stem cells. This proposal will provide a comprehensive database of toxicity of manufactured nanoparticles to stem cells and greatly enhance consumer confidence.