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方面具有巨大的潜力，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，设备，药物输送）。然而，首先必须面对一个重大挑战：理解和量化纳米颗粒特性与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一种材料整合到一个活的有机体中，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，具有自我更新和分化的能力。成体干细胞不断为我们的身体提供新的细胞系。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，突变细胞产生癌性肿瘤并维持肿瘤生长。我们之前的研究表明，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。在该提案中，将制造四种纳米粒子（碳、银、二氧化钛和氧化锌），并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颗粒对干细胞命运的影响，并开发出评估纳米颗粒健康和安全的方法，极大地增强消费者的信心。此外，这项研究将加强对代顿大学研究生和本科生的研究。

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.