Graduation Date

Spring 5-7-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Pharmaceutical Sciences

First Advisor

Aaron Mohs, PhD

Abstract

Bioimaging tools enable the visualization of small anatomical features as well as structures that may be obscured by other tissue. One such group of tools are fluorescent probes, molecules that emit detectable signals when stimulated by an excitation source. Incorporating fluorescent conjugates for clinical purposes would enable direct usage for the diagnosis, detection, or treatment of diseases. The development of specific targeting agents is feasible due to the number of nanomaterials and biological products that contain fluorophores. Specific targeting agents can target a particular region of interest, such as a cancerous tumor for removal or vital nerve structure for avoidance during image-guided surgery.

As a result, fluorescent guided surgery (FGS) allows a surgeon to remove or avoid specific areas during surgical interventions without damaging surrounding tissue or structures. Many different biomaterials, each with unique and useful properties, can be utilized as a platform for fluorescent contrast agent design, such as avoiding vital anatomical structures. During surgical intervention, the location of nerves is of high concern for surgeons, as damaging those structures can result in severe consequences for the patient. Herein, the fluorescent contrast agent NervelightTM, consisting of a near-infrared (NIR) fluorescent dye attached to the naturally occurring protein, nerve growth factor, can be utilized for nerve targeting and visualization. Nerves are at high risk for damage during surgery; avoidance of these areas is critical to preserving nerve function.

Nanomaterials can also be used as platforms for NIR dyes to target ligands bound at the cell surface providing tissue specificity. In this study, carbon or silica-based nanomaterials were used as a scaffold for imaging a CD44+ cancer cell line. A targeted fluorescent nanomaterial design may provide specific targeting to CD44+ cancerous tumors for surgical removal via hyaluronic acid, a known CD44 targeting ligand, and the NIR fluorophore sulfo-Cy5 dye. Fluorescent contrast agents can be useful in labeling an area for avoidance or surgical removal in bioimaging applications.

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