Yuan Wan

Graduation Semester and Year

2012

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering

Department

Bioengineering

First Advisor

Samir M. Iqbal

Abstract

Early detection and isolation of circulating tumor cells (CTCs) can enable early cancer diagnosis and more effective therapeutics. Aptamers have emerged as probe molecules that have binding affinities comparable to antibodies but specificities better than those of antibodies. Epidermal Growth Factor Receptor (EGFR) is the most frequently overexpressed receptor in all human malignancies. The expression levels of EGFR in cancer cells can be over 100 times higher than those in normal cells. It is an attractive target for cancer therapy and cancer cell isolation.This dissertation focuses on two different areas: developing strategies for anti-EGFR aptamer based cancer cell isolation, and studying its growth inhibitory activity to cancer cells. First of all, surface-bound anti-EGFR aptamers were demonstrated to capture human Glioblastoma (hGBM) cells and enrich hGBM cells from cell mixture. The ensuing work showed that nanotextured surfaces, which mimic the nano-scale topography of basement membrane showed increased sensitivity of capture. Furthermore, aptamer functionalized glass beads device was designed, modeled and fabricated to improve cell isolation sensitivity and specificity respectively. On the other hand, anti-EGFR aptamers were used to intercept the receptor tyrosine kinase (RTK) signal, and therefore inhibit hGBM cells proliferation and migration in vitro.In brief, the anti-EGFR aptamer can specifically recognize and capture EGFR overexpressing cancer cells, and it has significant inhibition effect on hGBM cells proliferation and migration in vitro. It can have important implications for chip-based cancer cell isolation and cancer therapy.

Disciplines

Biomedical Engineering and Bioengineering | Engineering

Comments

Degree granted by The University of Texas at Arlington

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