Investigations and Mitigation of Carbon Nanomaterial Toxicity

描述（申请人提供）：随着碳纳米管（CNT）的应用越来越丰富，生产需求也越来越大。由于这种活性的增加，人们对碳纳米管的毒性进行了大量研究。人们发现纳米管对人体具有毒性作用，包括炎症、氧化应激和细胞凋亡，类似于石棉。因此，需要开发一种从环境中去除这些有毒纤维的有效方法。我们在这里假设，通过使用酶催化，我们可以在环境和生理相关的设置中启动碳纳米管的降解。我们的初步数据表明，天然酶辣根过氧化物酶（HRP）以及低浓度的H2O2 （40 5M）可以降解这些纳米材料。我们还观察到，人髓过氧化物酶（hMPO）可以降解碳纳米管，说明了一种双管齐下的方法（环境和人类健康）。我们这个项目的具体目标包括：(1)确定影响HRP和hMPO降解碳纳米管动力学的环境和结构因素，(2)确定HRP和hMPO催化碳纳米管降解的分子机制，(3)确定HRP/hMPO降解碳纳米管的产物并评估其毒性。了解碳纳米管及其转化产物对人类健康的影响，包括其在环境和体内生物降解所必需的化学功能化，是本研究的重要终点。

DESCRIPTION (provided by applicant): As carbon nanotube (CNT) applications become more abundant, so do production demands. Because of this increased activity, much research has been performed in examining the toxicity of CNTs. Nanotubes have been found to exhibit toxic effects to the body including inflammation, oxidative stress, and apoptosis, similar to that witnessed from asbestos. As such, an effective method to remove these toxic fibers from the environment needs to be developed. We hypothesize here that by using enzymatic catalysis, we can initiate degradation of CNTs in environmentally and physiologically relevant settings. Our preliminary data shows that a natural enzyme horseradish peroxidase (HRP), along with low, local concentrations of H2O2 (40 5M), can degrade these nanomaterials. We have also observed that human myeloperoxidase (hMPO) can degrade CNTs, illustrating a two-pronged approach (environment and human health). Our specific goals for this project include (1) identifying environmental and structural factors affecting the kinetics of CNT degradation using HRP and hMPO, (2) identifying the molecular mechanism(s) of CNT degradation catalyzed by HRP and hMPO, (3) determining the products of HRP/hMPO- degradation of CNTs and evaluating their toxicity. The significant endpoint of this study will be marked by an understanding of the effects of CNTs and their transformation products on human health, including the necessary chemical functionalization for their biodegradation in the environment and in vivo. PUBLIC HEALTH RELEVANCE: Developments in nanotechnology vastly increase the demand and use of carbon nanotubes, correspondingly with their health hazards and toxicity to the environment. This dictates the necessity to develop approaches for safe removal of carbon nanotubes from the environment. This proposal outlines novel technologies and protocols for biodegradation of carbon nanotubes through enzymatic catalysis mitigating environmental and subsequent physiological toxicity from carbon nanomaterials.