Cytoxic and Genotoxic Effects of Manufactured Nanoparticles on Stem Cells

描述(申请人提供)：纳米技术在生物医学应用方面具有巨大的潜力，目前正在研究诊断(例如成像、传感器)和治疗(例如植入物、装置、药物输送)。然而，首先必须应对一个重大挑战：理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、表面化学和颗粒大小如何与材料整合到活的有机体中，特别是与敏感的细胞系统-干细胞，在很大程度上是未知的。干细胞是一种独特的细胞群体，具有自我更新和分化的能力。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，干细胞可能是突变细胞的来源，从而导致肿瘤的发生和维持肿瘤的生长。我们之前的研究表明，碳纳米管和纳米银颗粒可以在小鼠胚胎干细胞中诱导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)，并将评估其对干细胞的毒性。这项研究将有助于我们更好地了解纳米粒子对干细胞命运的影响，并开发评估纳米粒子健康和安全的方法，大大增强消费者的信心。此外，这项研究还将加强代顿大学研究生和本科生的研究。 与公共健康相关：纳米技术革命有可能超越工业革命，带来1万亿美元的收入。有必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，可以产生许多不同的细胞谱系。干细胞的功能和性质与体细胞有很大不同。干细胞的突变可能会导致癌症，并可能危及多个细胞谱系，并影响后代的福祉。该项目的目的是了解纳米粒子对干细胞命运的影响，并开发一种快速且经济有效的方法来确定制造的纳米粒子对干细胞的毒性。这项提议将提供一个关于人造纳米颗粒对干细胞毒性的全面数据库，并极大地增强消费者的信心。

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.