Development of Polyurethanes for Analysis and Treatment of Cancer Induced Bone Disease

Abstract

Overall cancer fatalities have stabilized since the early 1990s, however the prevalence of cancer is still remarkably high for men (45%) and women (38%). While the recent advances in treatments for cancers have increased the lifespan of patients, it has opened new doors to metastatic diseases that were not pathologically relevant in the past. One of the most prominent metastatic sites for common cancers is often the skeletal system. Skeletal metastasis increases mortality significantly, and cancer induced bone disease is associated with increased pain, hypercalcemia, and fractures. There are many possible factors that induce the phenotypic and genetic changes that occur when cancers metastasize to bone, effectively render the cancer incurable. One possible cause is the large difference in rigidity between bone and soft tissue of the primary site of tumors. The ability to study rigidity based effects in vitro is beneficial to gaining a better understanding of the complex microenvironmental interactions in cancer induced bone disease. The goal of this dissertation was to study polyurethane (PUR) based materials for cell culture system that could be utilized to study the effects of physiologically relevant rigidity in cancer induced bone disease and to develop novel strategies to deliver therapeutics with a combined platform for tissue regeneration and drug delivery. The PUR cell culture analysis was able to mimic the rigidity found in bone and soft tissues. The downstream targets identified by the previous study can be affected by several classes of small molecule hydrophobic drugs; however, the most effective drugs are insoluble in aqueous environments and have posed significant challenges in both systemic and local delivery to tumors. These challenges can be overcome with polycationic micellar nanoparticles which could be loaded into, injectable, PUR based bone grafts. Taken together, this work paves presents a path to develop PUR materials to study and ultimately treat cancer induced bone disease.