The Effect of Engineered Nanoparticles on Airway Epithelial Cells

Author(s): Tsai, Shih-Ming | Advisor(s): Chin, Wei-Chun | Abstract: Expanding interests in nanotechnology as applied to electronic and biomedical fields have led to the fast-growing development of various new and novel nanomaterials (NMs). Researchers have utilized the different sizes, shapes and, surface modifications of nanoparticles for various applications. Nanoparticles are a primary component used in all kinds of current commercial products that are closely related with our daily life. However, recent studies raise concerns about how these nanoparticles affect the environment and human health. It is therefore required to pay more attention to the health effects of new materials. The human airway system plays a crucial role in preventing hazardous environmental changes. The airway epithelial cell is the first barrier and activates the body’s defense mechanisms such as mucus secretion to buffer the immediate effects on the cell and provide the opportunity for the immunosystem to respond to further emergency situations. The overall object of this dissertation is to focus on how novel engineered nanoparticles interact with the airway epithelial cells and the response of the cells. Our studies were divided into two parts that provide the positive and negative results of different nanoparticles. These results suggested the possible hazardous routes nanoparticles can take to trigger cytotoxicity. On the other hand, our results also suggested some nanoparticles can also eliminate certain types of toxicity effects by different kinds of nanoparticles. Our results systematically used various different techniques to guide the methods used to study the nanotoxicity of nanoparticles. Graphene is a single-atom thick, two-dimensional sheet of hexagonally arranged carbon atoms with unique physical and chemical properties. Recently, graphene has been used in many studies on electronics, photonics, composite materials, energy generation and storage, sensors, and biomedicine. However, the current health risk assessment for graphene has been relatively limited and inconclusive. Our first aim is to evaluate the toxicity effects of graphene on the airway epithelial cell line BEAS-2B, which represents the first barrier of the human body to interact with airborne graphene particles. The result showed that graphene could induce the cellular Ca2+ by the activation of EGFR (epidermal growth factor receptor), and the pathway associated with PLC (phospholipase C). Subsequently, IP3 (Inositol 1,4,5-triphosphate) receptors activate the release of Ca2+ from the ER (Endoplasmic Reticulum) Ca2+ stores. Those Ca2+ signals further trigger the calcium-regulated apoptosis in the cell. Furthermore, graphene stimulation can cause EGFR upregulation, which has been demonstrated to associate with diseases such as lung cancer, COPD (chronic obstructive pulmonary disease), and cardiovascular diseases. This study highlights the additional health risks that may pose as contributing factors to other respiratory diseases. Another aim of our studies is to determine the ability of CeO2 NPs to protect the airway epithelial cells by the stimulation of TiO2 NPs. The exposure of nanoparticles can induce hypersecretion and accumulation of airway mucus that are closely associated with many respiratory diseases. Titanium dioxide (TiO2), one of the PM10 components, is a major NP that is widely utilized in many commercial products. Our previous study established the connection between induced airway mucus secretion and TiO2 NPs. However, the countermeasure to reduce the harmful effects of TiO2 NPs, especially airway mucus secretion, remains unexplored. One of the potential candidates to reduce airway mucus secretion is Cerium Oxide (CeO2) NPs. It has been reported that CeO2 NPs could protect cells by diminishing ROS and inflammatory responses. Herein, our study shows that CeO2 NPs can reduce the cytosolic Ca2+ changes and mitochondrial damages caused by TiO2 NPs. Our results provide the evidence that CeO2 NPs can attenuate hypersecretion of mucus and apoptosis progression induced by TiO2 NPs. This study highlights the potential capacity of CeO2 NPs as supplementary material for TiO2 NPs applications in the future.