Date on Master's Thesis/Doctoral Dissertation

8-2018

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Frieboes, Hermann

Committee Co-Chair (if applicable)

Steinbach-Rankins, Jill

Committee Member

Steinbach-Rankins, Jill

Committee Member

El-Baz, Ayman

Committee Member

Rouchka, Eric

Committee Member

Hood, Joshua

Author's Keywords

cancer; biological modeling and simulation; nanotherapy; nanoparticle; chemotherapy; cisplatin

Abstract

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.

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