Colorectal cancer (CRC) is the second leading cause of cancer-related deaths and the fourth most common cancer in the United States. When CRC disseminates into the abdominal cavity, there can be hundreds, if not thousands, of small tumors infiltrating the surfaces of organs, making it extremely difficult to treat by conventional methods. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in combination with cytoreductive surgery (CRS) has improved the 5-year survival rate of late-stage CRC patients from 12% to 51%. However, the survival rates of these patients have stagnated, which emphasizes the need for more innovative approaches to improve patient survival outcomes.

The purpose of this dissertation was to assess an adjuvant nanoparticle therapy that could aid in targeting and treating micro-sized tumors in a disseminated colorectal cancer model. We hypothesized that polymer nanoparticles, synthesized from PCPDTBSe and PFBDTBT10 blends, with surface targets (hyaluronic acid) would bind specifically to CD44+ surface CRC tumors and cancer cells in vivo. The nanoparticles developed here, designed to target the cancer stem cell marker CD44, allowed for visualization of the tumor locations and possessed the ability to generate on-demand local ablative heating to treat small tumors. The nanoparticles were perfused throughout the abdominal cavity of mice with disseminated colorectal cancer to bind small and micro-sized disease. This dissertation will outline the development and properties of the nanoparticles utilized for the described experiments, the results from the disseminated murine model applying this nanoparticle perfusion system, and the impact this data has for future clinical treatments of disseminated abdominal cancers.