Date of Award
Doctor of Philosophy (PhD)
Chemical and Biomolecular Engineering
Dennis E. Discher
Key questions in this study are how to shrink tumors in vivo and what physical property of cancer cell determines tumor invasiveness. Delivery of drug molecules to distant tumor tissue in the body is the highest challenge in any types of cancer therapies, and this goal was approached from two aspects in the first half of the study, namely using worm-like shaped drug delivery vehicle or Filomicelle and adding protein CD47 to the vehicle surface, which can send a stop signal to macrophage phagocytosing a foreign material. Drug-loaded Filomicelles applied for brain tumor treatment in combination with radiation therapy to obtain the access inside brain tissue by disrupting blood brain barrier. CD47-attached particle was tested for accumulation in tumor tissue, followed by subcutaneous tumor shrinkage study. Second half of the study focuses on cell nuclear physics in the context of cell migration and tumor progression as a physiological example where cell migration plays an essential role for progression. Nuclear stiffness was controlled by changing the expression of Lamin-A,C, a protein forming mesh struture underneath inner nuclear membrane to give a physical strength the nucleus. Relative expression of Lamin-A,C to its isoform Lamin-B nicely predicts behavior of nuclear shape after stress application and importantly cell migration sensitivity against Lamin-A,C change through physically constraining environment. This observation leads to quite simple viscoelastic model in which Lamin-A,C and -B are responsible for nuclear viscosity and elasticity, respectively.
Harada, Takamasa, "From Engineering of Tumor Shrinking Dds to Engineering the Nucleus for Tumor Growth" (2013). Publicly Accessible Penn Dissertations. 761.