| Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. According to the American Cancer Society, there is a five-year survival rate of only 5% once diagnosed with this deadly disease, and while surgery, radiotherapy and traditional chemotherapy are all options for the cure, they seldom do more than extend survival and relieve symptoms. Additionally, pancreatic cancer is often already at an advanced stage when diagnosed, mainly due to the asymptomatic character in the early stages of the disease as well as lack of early detection methods.;Gemcitabine, the standard chemotherapeutic drug used to treat advanced stages of pancreatic cancer, only prolongs life marginally and relieves symptoms. It and other chemotherapeutic agents are characterized by their short half-lives and low therapeutic indices. While the administered chemotherapeutic drugs are meant for malignant cells, the drugs do not have the ability to specifically target them in vivo; therein lies the many unfortunate side effects due to the attack of normal cells.;This research project is focused on targeted drug delivery. For this purpose, gold nanoparticles (GNPs) are used as the platform, since they enhance passive tumor targeting via the enhanced permeability and retention effect, and the transferrin (Tf) protein is used as an active cellular targeting moiety. As transferrin receptors are upregulated on the surface of 93% of pancreatic cancer cells, the transferrin protein is an excellent candidate as the targeting moiety. Herein, poly(propylene imine) (PPI) dendrons have been designed, prepared, and conjugated with Tf and used to decorate the surface of GNPs. Moreover, the conjugation of gemcitabine to PPI dendrons has been attempted through pH sensitive bonds, and other approaches are being considered for future work.;The long-term goal of this research project is to produce a new type of multifunctional nanocarrier with the intention and expectation to increase the effectiveness of the delivered chemotherapeutic agents during treatment of patients with pancreatic cancer. This will presumably decrease the toxicity and drug resistance associated with conventional chemotherapeutic agents, as well as decrease the chemotherapeutic dose. |
