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.

Public Health Relevance

Despite effectiveness of transarterial chemoembolization (TACE) in Hepatocellular carcinoma (HCC), TACE remains non-curative with high recurrence rates. In this project, our recently developed glucose oxidase-based theranostic nanoplatform, synergizing reactive oxygen species (ROS) generation with tumor glucose depletion, will be combined with trans-arterial delivery technology to maximize targeted delivery to HCC with a significantly improved therapeutic profile, reducing systemic toxicity associated with traditional intravenous administration.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA249828-01A1
Application #
10128242
Study Section
Drug Discovery and Molecular Pharmacology Study Section (DMP)
Program Officer
Fu, Yali
Project Start
2021-03-01
Project End
2023-02-28
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
1
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239