Pancreatic cancer (PC) is a devastating disease with a dismal prognosis. It is the 4th most common cause of cancer death in the Western world, with a 5 year survival rate <6%. Typically PC is characterised as being resistant to chemotherapy and highly metastatic. In fact, the best drug treatments only prolong life by 16 weeks. We have identified a highly promising therapeutic target - βIII-tubulin, which when inhibited using RNA interference (siRNA/shRNA) agents increased sensitivity to chemotherapy drugs and reduced tumour growth and metastases in a clinically relevant PC mouse model 1. While these results are highly encouraging, unfortunately there are no pharmacological inhibitors for βIII-tubulin, and delivery of siRNA as a therapeutic agent requires a vehicle. Recently our group generated cationic star polymer nanoparticles which complexed and delivered siRNA to PC cells in vitro 2. Moreover, we showed that cationic star polymers may be used for local delivery of siRNA to tumour cells in vivo 2. Despite their clinical potential, most cancer therapeutics require systemic administration in an effort to target both primary and metastatic tumour sites. A limitation of cationic nanoparticles for systemic delivery of siRNA is their toxicity and potential to activate the immune system 3. The incorporation of polyethylene glycol (PEG) onto the surface of nanoparticles has been shown to be an effective strategy for overcoming these challenges 3. We have now modified the surface of our star nanoparticle to allow for increased tumour retention and stability in the blood via the addition of PEG. Our encouraging results demonstrate that our star-PEG nanoparticle can deliver siRNA following systemic delivery to tumours growing within the pancreas. These technologies have the potential to deliver siRNA agents to pancreatic tumours and increase the efficacy of chemotherapy, which may increase PC patient survival.