Date of Award

Spring 2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

First Advisor

David Kish Mills

Abstract

The National Cancer Institute and the American Cancer Society estimate that 1.6 million new cancer incidences and over half a million cancer related deaths occur annually [1][2]. Cancer the second most common cause of death in the United States [1], [2]. Although the causes of cancer can vary depending on cell type, all or almost all instances of cancer arise from a mutation or from an abnormal activation of the cellular genes that control cell growth and mitosis [3].

Treatment of a given cancer type depends on the subtype, stage and progression of the cancer. Varieties of cancer therapy include surgery, immunotherapy, radiation therapy, chemotherapy, hormone therapy, targeted therapy, gene therapy and stem cell transplant [4]. Some treatments help patients achieve remission, and with additional treatment, can cure the illness. Many of the available therapies have drawbacks that can negatively affect patients. Some of these drawbacks include systemic, as opposed to local, delivery of chemotherapeutic agents, pain, hair loss, reoccurrence and metastasis post-surgery.

A major goal of current research in cancer medicine is to develop novel strategies and materials to halt the advance of cancer and its potential metastasis. This goal can be achieved by employing strategies that can localize treatments to affected areas, sustaining drug release to these areas, and destabilizing cellular processes that affect cell-drug interaction.

The focus of this dissertation was to design and develop novel injectable and implantable applications for gene and chemotherapeutic cancer treatment. The use of naturally occurring materials can improve gene and drug delivery characteristics in vivo. The research aimed to establish halloysite nanotubes as a novel delivery system for drugs and/or genes. The first stage of this goal was to analyze the drug and gene release by establish a release profile from halloysite nanotubes. The next stage was in vitro assay to determine the transfection efficiency of pIRES2-EGFP loaded Halloysite Nanotubes (HNTs), and the and in vitro cell proliferation and cytotoxicity assay of methotrexateloaded HNTs. Results indicate that methotrexate-or pIRES2-EGFP loaded nanotubes, and composite films can boost transfection efficiency and reduce cancer cell growth and proliferation. Nanotubes showed promise in gene delivery as they enhanced the transfection efficiency of commonly used transfection reagents. Nanotubes and nanotubeimbedded films show promise as novel chemotherapeutic treatments as the provided a platform for sustained and localized drug delivery in vitro.

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