Semester

Spring

Date of Graduation

2013

Document Type

Thesis

Degree Type

MS

College

Statler College of Engineering and Mineral Resources

Department

Chemical and Biomedical Engineering

Committee Chair

Cerasela Zoica Dinu

Committee Co-Chair

Linda Sargent

Committee Member

Yong Yang

Abstract

As the applied use for carbon nanotubes (CNTs) increases across engineering and biomedical sectors, a clear understanding of the deleterious effects surrounding CNT-induced toxicity, namely genotoxicity, is required. Currently, the exact genotoxic mechanisms that surround CNT-induced mitotic disruption that result in aneuploidy are not completely understood. Thus, there is a need for clear mechanical models to be formulated. Herein a comprehensive overview of the nanotube toxicity is provided insisting on the aspects related to CNTs genotoxicity.;In Chapter 1, I am providing a review of the current research in the CNT-s induced toxicity. I start by defining these members of the fullerenes family and subsequently talk about their implementation in a variety of applications from interconnects to composite polymers, from electrodes to high temperature fillers, from bioimaging to biosensors, and finally in drug delivery. Next, I introduce aspects related to the CNT toxicity in vitro and in vivo, both in relation to the cytotoxicity and genotoxicity specifically focusing on what is currently known about CNT-induced genotoxicity and suggesting more research in the area of critical mitotic mediators i.e. the cytoskeletal filament, microtubules and their associate mitotic molecular motors, while also proposing an application for CNT use in targeted drug delivery, respective of molecular motor targets. Lastly, my Chapter focuses on the current research in CNTs-induced genotoxicity and proposes a more exact model of the aneuploidy that could take place upon cellular exposure. Such findings could lead to designing novel CNT-based platforms to improve chemotherapeutic efficiencies for targeted delivery and cancer therapeutics. However, this Chapter also points out that the goal for CNT use in cancer therapy will require convergence to minimize host cytotoxicity, while maximizing cancer cell genotoxicity.;In Chapter 2, I describe functionalized MWCNT-induced mitotic disturbances following in vitro exposure of BEAS-2B, human bronchial epithelial cells. I present distinctly different characterizations between the degree of MWCNT functionalization and how that affects the cellular response. Following cell treatment changes in the cell cycle have been observed, resulting in cell cycle arrest, that correlate with changes in mRNA expression of molecular motors, dynein and Eg5, resulting in a reduction of total protein expression in a time dependent manner. This study is the first to show MWCNT-induced disruptions of critical mitotic mediators, i.e. molecular motor proteins dynein and Eg5, and one of several studies that confirm clear disruptions in the cell cycle following exposure to functionalized MWCNTs, thereby providing a viable mechanical model for the CNT-induced genotoxicity.

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