Nanoparticle margination, adhesion, and uptake in microflow

Abstract

Various nanoparticles have been investigated as drug carriers for delivery to diseased cells in the body. Targeted delivery of nanocarriers specifically to diseased cells can help to shield collateral cells from harmful cytotoxic drugs and reduce the many harmful side effects associated with chemotherapy. Recent advancements in our understanding of the complex behavior of intravenously injected nanoparticles has informed the rational design of the next generation of tailored nanocarriers. However fundamental questions about the mechanisms driving the behavior of nanoparticles in vasculature remain. Phenomena important for particle margination, adhesion, and uptake as well as the dependence of each on nanoparticle characteristics such as size and shape still remain elusive. This dissertation reports an experimental study of the effects of size and shape on polymeric nanoparticle margination and uptake in bare and cell-containing microfluidic environments, respectively. It is found that the competition of Brownian force and electrostatic repulsive forces between particles near the wall and adhered particles on a bare glass substrate lead to insensitive size dependence of spherical particles on margination and adhesion propensity. With the presence of cells on channel walls and a reduced zeta potential, however, the repulsive force is reduced such that a dominant Brownian force leads to more uptake of smaller spherical particles in shear-adapted endothelial cells. In comparison, increased flow-driven rotation of non-spherical nanoparticles with increased size and aspect ratio enhances particle/cell interaction frequency which dominates the effect of Brownian motion and the energy for membrane deformation, leading to more uptake of larger and larger-aspect ratio non-spherical nanoparticles in shear adapted endothelial cells.