Title: SPIO-GOx conjugate for transarterial liver cancer therapy Abstract: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and ranks third amongst cancer-related deaths, with over 700,000 new cases diagnosed each year. Improved therapies for this disease is urgently needed. Cancer cells die in three ways: apoptosis, necrosis and autophagy. A significant increase in intracellular reactive oxygen species (ROS) can cause irreversible oxidative damage, leading to cell death through both apoptosis and necrosis. Recently, our team created a novel SPIO-GOx nanoplatform, synergizing ROS and metabolic depletion therapies. Using in vitro and in vivo studies, we found this nanoplatform could produce very high levels of ROS and highly efficient tumor cell destruction. Maximizing the therapeutic profile of this agent through targeted delivery and minimal systemic toxicity will be crucial for effective clinical translation. Transarterial chemoembolization (TACE), where chemotherapy is delivered directly into tumor-feeding arteries, is the current standard of care for unresectable HCC. TACE synergizes delivery of chemotherapy with embolization of tumor blood vessels while significantly minimizing toxicity due to targeted delivery. In this project, we plan to leverage our innovative SPIO-GOx theranostic nanoplatform with trans-arterial delivery technology to investigate the potential application in liver cancer treatment. If successful, we may advance the science of liver cancer treatment using this novel theranostic nanotherapy.