Date of Award
Doctor of Philosophy
Paul M. Dalhaimer
Eric T. Boder, Paul D. Frymier, Patricia N. Coan
Since almost 70% of the U.S. population over 20 years old is overweight and 30% is obese, with much of the western world following suit, many patients that will potentially be administered circulating nanoparticles designed to localize to tumors and avoid non-target areas will have significant amounts of white adipose tissue (WAT), enlarged livers, and additional metabolic complications such as type 2 diabetes. However, studies on nanoparticle biodistribution and efficacy take place almost without exception in lean rodents with healthy metabolic states. In this work, I determined the biodistribution of model nanoparticles – neutral filomicelles and polystyrene spheres both carrying near infrared (NIR) dye - as a function of mouse diet, weight, and metabolic condition. The livers of diet-induced obese mice show increased uptake of nanoparticles, while mice with non-alcoholic fatty liver disease (NAFLD) do not see increased uptake despite livers that are four fold as massive. Macrophages and hepatocytes had increased particle internalization in vitro in media with increasing amounts of fatty acids. From these observations, I postulate that the metabolic condition of the patient will change the efficacy of current nanoparticle technologies.
Quigley, Kevin James, "Elucidating the effects of metabolic state on nanoparticle distribution in mice and in vitro uptake. " PhD diss., University of Tennessee, 2016.