Download or read book Contribution of Engineered Nano-materials Biological and Physicochemical Properties to Cellular Stress and Toxicity written by Indushekhar Persaud and published by . This book was released on 2017 with total page 143 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nanoparticles (NPs) are becoming more commonly used in numerous consumer and medical applications, thereby increasing human exposure. To name a few uses, NPs are utilized as protective and antibacterial coatings, drug delivery vehicles, electronics, medical imaging, treatment of a wide range of diseases, cosmetics, and tissue engineering [1-8]. NPs are also found as a manufacturing byproduct and found from combustion processes, which poses a health hazard [9, 10]. The Food and Drug Administration (FDA) defines NPs as particles with a size of 1 - 100 nm, and the toxicity guidelines state they are documented as adaptive and flexible. Due to the rapid development of nanotechnology, the number of NPs exceeds our capability for testing their toxicity, thereby necessitating an understanding of the general mechanisms of their toxicity. The size range of NPs allows them to have unique interactions with proteins and cells, thus making them ideal for their development as therapeutics and imaging contrast agents in medical applications. The potential of using these NPs depends on fully characterizing their toxicity and adverse interactions with biological systems. The purpose of this dissertation study was to understand the role of key physicochemical properties (e.g. biocorona and chemical defects) of NPs on cellular stress and the subsequent toxicity. The first aim of this study examined the formation of a biocorona (BC) on silver nanoparticles (AgNPs), and their contribution to endoplasmic reticulum (ER) stress. Once a NP enters the blood stream or other biological fluids, proteins will form a corona around the NPs resulting in a new biological entity which then affects their interactions with various cells and tissues. Two BCs that were investigated are modeled after common circulating proteins that have been shown to interact with AgNPs; bovine serum albumin (BSA) and high-density lipoprotein (HDL). In addition, I used fetal bovine serum (FBS) to serve as a model for a complex corona comprised of multiple proteins and lipids attached to NPs. The results of hyperspectral imaging and dynamic light scattering showed that proteins bind to AgNPs. In addition, circular dichroism spectroscopy showed that the structure of the proteins is perturbed when associated with NPs. Importantly, AgNPs induce ER stress responses in endothelial cells through activation of the IRE pathway. Further, the presence of a BC on AgNPs modified the ER stress response which varied according to the composition of the BC. Lastly, I observed differences in the subcellular localization of NPs due to size differences that likely contributed to the ER stress response. The second aim of this dissertation was to examine the contribution of chemical defects in ZnO NPs to cellular stress and toxicity. Due to the manufacturing process, contaminants may be incorporated into the crystal structure of NPs resulting in changes in their physicochemical properties. The results of this study indicate that chemical defects modify the degree of ER stress and oxidative stress in endothelial cells. In contrast to AgNPs, ZnO NPs induced ER stress through the PERK pathway, and the response is enhanced by oxidation of ZnO NPs compared to pristine ZnO NPs with no chemical defects. Furthermore, the cellular redox potential was reduced in endothelial cells exposed to ZnO NPs with defects compared to cells treated with pristine ZnO NPs. I conclude that the interactions of NPs with proteins as well as chemical defects of the NPs contribute significantly to cellular stress and toxicity. Taken together, the results indicate additional physicochemical properties such as chemical defects and BC formation contribute to cell stress and toxicity and should be considered when screening for the safety of NPs for consumer and medical applications.