Faculty News
"Development of Targeted Polymeric Pro-drugs for Treatment of Liver Cancer"
Mohamed El-Sayed, PhD; William Ensminger, MD; and Donna Shewach, PhD
2008 funding: $100,000
Though liver cancer is the fifth most common cancer in the world accounting for approximately one million new cases per year, the treatment options that exist are either highly invasive, or have limited specificity towards cancer cells and in all cases they fail to improve the survival of liver cancer patients. Being able to target liver tumors with a innovative drug delivery system, which can selectively shuttle a high dose of anticancer drug molecules into hepatic cancer cells and achieve the desired cancer cell death, would be an ideal solution to dealing with this deadly disease. In this early-stage project, the team is developing a drug delivery system using novel polymer-drug conjugates for treatment of primary liver cancer particularly hepatocellular carcinoma (HCC).
Using funds provided by the U-M's Coulter Program, the project team proposes to conjugate a chemotherapeutic agent to water-soluble polymers, namely poly(amido amine) (PAMAM) dendrimers via covalent hydrolysable linkages to prepare nano-sized, water-soluble conjugates for treatment of HCC. These polymer-drug conjugates will target the "leaky" blood vessels supplying the tumor structure to preferentially diffuse and accumulate in cancer tissue. Once inside the tumor tissue, the targeting ligands displayed on the surface of polymer-drug conjugates will trigger individual cancer cells to draw these conjugates inside the cell. Once inside the cell, enzymes specific to liver cancer cells will break the linkage between the polymeric carrier and the chemotherapeutic drug. The free drug will kill the cancer cell and the carrier will be eventually excreted in urine. This is cell-specific delivery of chemotherapeutic drugs.
Currently, non-surgical treatment options for HCC patients have failed to improve their survival, which remains less than 12 months. These statistics indicate the urgent clinical need for alternative treatment options with improved therapeutic outcomes. Successful development of the proposed conjugates will provide a new treatment strategy with a significant commercial potential particularly with the increasing number of patients diagnosed with primary liver cancer each year. In addition, this strategy can be further exploited for delivery of other classes of drug molecules for treatment of hepatic cancer.
A list of all the U-M Coulter funded projects is found on the UM BME Coulter Site.
Posted on July 7, 2008, 9:03 am