SBIR Phase II: Scaling up the Synthesis of Novel Poly(ethylene glycol) Based Dendrimers for Targeted Drug Delivery Applications

This Small Business Innovation Research Phase II project is aimed at the design and manufacture of agents useful for the diagnosis and treatment of breast and other cancers. The primary product is a novel water-soluble molecule constructed from poly(ethylene glycol) (or PEG), containing multiple arms with folate groups as well as a diagnostic agent. The folate groups will target cancer cells preferentially over healthy cells and the fluorescent diagnostic agent will allow effective breast cancer diagnosis. This targeting molecule differs from currently available materials in that the length and number of the PEG arms as well as the attachment of folate groups can be very carefully and reproducibly controlled, addressing a critical weakness with previous multifunctional devices. The precision synthesis steps are catalyzed by an enzyme, leading to very pure products. Currently three folate-targeted diagnostic molecules are in Phase III clinical trials, but all are based on small molecules and a single folate targeting group. The advantage of a polymer-based device with multiple folate groups will be a longer circulation time in the body with more effective targeting of cancer cells. The broader impact/commercial potential of this project is significant since by 2020 approximately 18.2 million Americans will be diagnosed with cancer. Breast cancer is the most frequently diagnosed cancer in both white and African-American women. One in eight American women develops breast cancer, and a new patient is diagnosed in every three minutes. Chemotherapy has many side effects such as hair loss and nausea, and requires extended patient care. Specific targeting is a significant advantage for diagnostic and chemotherapeutic agents. When a drug is delivered directly to the cancer cell to kill it, the collateral damage of healthy cells is minimized. New delivery devices are badly needed for cancer diagnosis and therapy, and if successful this project will provide both a new diagnostic agent as well as a platform technology for additional products. Another impact of this project is the use of an enzyme-catalyzed green manufacturing process which minimizes wasteful by-products. In the longer term, the market potential will be significant as the technology is adapted to specific diagnostic and therapeutic products.