Ultrasound-Targeted Drug Delivery for Treatment of Hepatocellular Carcinoma

Despite big advances in disease management, hepatocellular carcinoma (a primary liver cancer) remains the second most common cause of cancer death worldwide. Indeed, 50% of hepatocellular carcinoma patients suffer from intermediate and advanced disease due to resistance to current anti-cancer drugs, lack of tools to detect very early disease, and underlying liver disease that limits the use of drugs. Anticancer treatment is highly dependent on the delivery of the drug to the tumor. Selective delivery should increase the toxicity for the tumor while reducing side effects for the surrounding normal tissues. Ultrasound is a modality that is traditionally used for imaging and can be combined with ultrasound contrast agents for perfusion imaging. Using ultrasound of higher energy, contrast agents can be activated and interact with the surrounding tissue to induce tissue permeability and increased uptake of free-circulating drugs. We propose to use locally limited ultrasound exposure for a targeted activation of contrast agents and selective delivery of anti-cancer drugs. This ultrasoundtargeted drug delivery approach will be studied in the context of advanced hepatocellular carcinoma to provide a new technically feasible treatment approach that enhances survival.