Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Pharmacology and Toxicology, MS
Committee Co-Chair (if applicable)
cancer; biological modeling and simulation; nanotherapy; nanoparticle; chemotherapy; cisplatin
The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug strength affects the proportion of proliferating, hypoxic, and necrotic tissue fractions, which in turn dynamically affect and are affected by the vascular density. This study establishes a first step towards a more systematic methodology to assess the effect of vascular-induced tumor tissue heterogeneity on the response to nanotherapy.
Miller, Hunter Allan, "Evaluation of drug-loaded gold nanoparticle cytotoxicity as a function of tumor tissue heterogeneity." (2018). Electronic Theses and Dissertations. Paper 3050.