Modeling of vascular tumor growth: Microenvironmental fluid dynamics, nanotherapeutics delivery and chemotherapy

One of the most critical components in the tumor micron-environment that affects transport of nutrient/therapeutical agents. Interstitial fluid provides a means of delivering materials to the cells, intercellular communication, as well as removal of metabolic wastes. The interstitial fluid pressure (IFP) is found to be zero or negative in normal tissue owing to functional lymphatic drainage. In normal tissues, the blood enters the local capillary via arterioles and travels following the pressure drop leaves the tissue through the venous or lymph networks. As blood flows, it exchanges via the permeable vascular wall with the fluid outside of the vessels which is called interstitial fluid or tissue fluid leave the tissue through the lymphatic vessels or by refiltrated back to the blood. In tumor microenvironment, however, elevated interstitial fluid pressure is observed, and often is different in the tumor and host. In the tumor interior there is often a plateau in the IFP, which provides a transport barrier in nutrient or therapeutical agent delivery. Both theoretical and experimental studies have been performed to investigate IFP with a static tumor and vasculature. In this thesis, IFP, and vascularized tumor growth are coupled dynamically and the interplay between tumor and vasculature in terms of the microenvironmental fluid dynamics and nutrient/drug transport are under investigated. In chapter 1, we first incorporate the microenvironmental hydrodynamics into a hybrid vascular tumor growth model and investigate the effect of interstitial fluid pressure on tumor growth together with the collapses of blood/lymphatic vessels. In chapter 2, we apply the tumor model with a model of nanotherapeutics and study the drug temporal and spacial dynamics together with the chemotherapy output. In chapter 3, we develop agent transport equations in the hybrid vascular tumor growth model in chapter 1 that quantitatively track the drug bioavailability and illustrate the effect of vascular pathologies on therapy outputs. In chapter 4, we study the effect of nanoparticle design on nanoparticle distribution and chemotherapy in a growing tumor vasculature.