(110e) Cancer Treatment Using Drug Delivery Nanoparticles

In tumors, pores of size on the order of 100nm develop in the microvasculature wall due to abnormal endothelial growth. Drug delivery to these tumors via nanoparticles involves two physical processes: migration of nanoparticles to the endothelial wall (macroscale) and extravasation of these particles through the vasculature pores (microscale). Recent studies show that the treatment efficiency depends on nanoparticle shape and size specific to each tumor type, characterized by microvasculature geometry, pore size distribution and associated flow properties such as shear rates and oncotic pressure. We attack the two scales of the problem separately. As our preliminary model for the micro-scale, we develop a singular perturbation theory as well as develop a Brownian dynamics simulation to evaluate the pore-extravasation (flux) rate of point Brownian particles through a circular pore when they are in the presence of shear flow and pressure-driven suction flow (Sampson flow). Predictions from the Brownian dynamics simulation are found to agree well with our theory at the physiologically relevant range of Peclet numbers and suction strength. We then extend the validated Brownian dynamics simulation from point particles to finite sized spherical and rod shaped particles, and interface these simulations with a large-scale computational model for blood and nanoparticle transport in a model tumor microvasculature. With this, we demonstrate the capability to detemine nanoparticle leakage rates and how it varies depending on tumor type. We identify Brownian motion as a major deteminant in treatment efficiency and we characterize its effect, coupled with other flow parameters on the treatment efficiency for different tumor types.