Date of Award

12-17-2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Maged Henary, Ph.D.

Second Advisor

Donald Hamelberg, Ph.D.

Third Advisor

Suazette Mooring, Ph.D.

Abstract

This dissertation focuses on two fundamental yet unanswered questions in human health and disease concerning both diagnostics and therapeutics. The first half addresses the lack of optimized near-infrared fluorophores for image-guided surgery. Fluorescence imaging cameras and intraoperative imaging systems lack appropriately engineered contrast agents that allow the detection of sensitive normal tissue (i.e. endocrine and exocrine glands) for surgical avoidance. After systematically probing various fluorophore classes, we discovered promise in cyanine-based contrast agents. By altering functional groups of cyanine fluorophores, we, for the first time, report the selective targeting of many endocrine glands, exocrine glands, cartilage and bone using NIR fluorescence to visualize the targeted tissue. Secondly, this dissertation elaborates a new pathway for developing functional and fluorescent chemotherapeutics based on the targeting, stabilization and imaging of G-quadruplex DNA – a folding pattern commonly associated with cancer cell proliferation through telomerase over-expression and oncogene promoter regions. Chromophores modified to assume quadruplex binding characteristics – planar cationic structures – have been developed that stabilize the quadruplex as evaluated through several complementary methods toward developing novel theranostic agents in the NIR visualization and treatment of human cancers.

Available for download on Sunday, November 19, 2017

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