Date of Award

Winter 2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

First Advisor

Patrick O'Neal

Abstract

More than a decade into the development of gold nanoparticles, with multiple clinical trials underway, ongoing pre-clinical research continues towards better understanding in vivo interactions. The goal is treatment optimization through improved best practices. In an effort to collect information for healthcare providers enabling informed decisions in a relevant time frame, instrumentation for real-time plasma concentration (multi-wavelength photoplethysmography) and protocols for rapid elemental analysis (energy dispersive X-Ray fluorescence) of biopsied tumor tissue have been developed in a murine model. An initial analysis, designed to demonstrate the robust nature and utility of the techniques, revealed that area under the bioavailability curve (AUC) alone does not currently inform tumor accumulation with a high degree of accuracy (R2=0.56), marginally better than injected dose (R2=0.46). This finding suggests that the control of additional experimental and physiological variables (chosen through modeling efforts) may yield more predictable tumor accumulation. Subject core temperature, blood pressure, and tumor perfusion are evaluated relative to particle uptake in a murine tumor model. New research efforts are also focused on adjuvant therapies that are employed to modify circulation parameters, including the AUC, of nanorods and gold nanoshells. Preliminary studies demonstrated a greater than 300% increase in average AUC using a reticuloendothelial blockade agent versus control groups. Given a better understanding of the relative importance of the physiological factors that influence rates of tumor accumulation, a set of experimental best practices is presented. This dissertation outlines the experimental protocols conducted, and discusses the real-world needs discovered and how these needs became specifications of developed protocols.

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