Cancer cells

This thesis reports the development of a novel drug delivery system consisting of hollow nanoparticles, formed from manganese dioxide (δ-MnO2) sheets, that are coated with polydopamine and folic acid to selectively target cancer cells. The biodegradability and colloidal stability of the uncoated hollow nanoparticles were investigated in comparison to solid MnO2 nanoparticles and graphene oxide sheets. The MnO2 hollow nanoparticles degraded at a faster rate and seem to have a higher surface area and better colloidal dispersion than solid MnO2 nanoparticles. Xanthan gum was proven to improve colloidal dispersion of these hollow nanoparticles and were used for further cell studies. In this study, cancer and healthy cells were treated with coated hollow nanoparticles, and results indicate that this novel hollow nanoparticle may preferentially target and kill cancer cells. Particle aggregation has shown to be toxic to cells. Further studies with this novel drug delivery system may lead to a groundbreaking solution to targeted cancer therapy.

The function and role of PAK6, serine/threonone kinase, in cancer progressionhas not yet been clearly identified. Several studies reveal that PAK6 may participate in key changes contributing to cancer progression such as cell survival, cell motility, and invasiveness. Basedon the membrane localization of PAK6 in prostate and breast cancer cells,we speculated that PAK6 plays a rolein cancer progression cells by localizing on the membrane and modifying proteins linked to motility and proliferation. We isolated the raft domain of breast cancer cells expressing either wild type (WT), constitutively active (SN), or kinase dead PAK6 (KM) and found that PAK6 is a membrane associated kinase which translocates from the plasma membrane to the cytosol when activated. The downstream effects of PAK6 are unknown ; however, results from cell proliferation assays suggest a growth regulatory mechanism.

Anticancer drugs, including nocodazole and vinblastine, work by disrupting the dynamics of microtubules. Unfortunately, these drugs often produce numerous side effects, including nausea, vomiting, loss of appetite, loss of hair, increased chance of infection, and fatigue. My thesis research evaluated the efficacy of using repeated low doses of microtubule drugs instead of a single high dose, in an attempt to minimize side effects. Using nocodazole and vinblastine, I first established the minimum effective concentration that disrupts the microtubules in normal human cells grown in vitro and treated cells with those concentrations over a period of several days. I found that microtubules were increasingly depolymerized as the days progressed. Next, I tested a combination of nocodazole and vinblastine at low concentrations.