Scaling up the Synthesis of Novel Poly(ethylene glycol) Based Dendrimers for Targeted Drug Delivery Applications (NSF Phase II SBIR to Enzyme Catalyzed Polymers LLC; subcontract to the Puskas group)

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) (PEG for short), 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 the ability to increase the targeting effectiveness and have a longer circulation time in the body. The product will be optimized in collaboration with the Imaging Group of the Cleveland Clinic.

The broader impact/commercial potential of this project is significant since by 2020 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. Systemic treatment by chemotherapy has many side effects such as hair loss and nausea, and requires extended patient care.  Specific targeting is the optimal approach for any diagnostic and chemotherapeutic agent. When the 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 therapy. Our work has been publicized and generated interest in the local community. With the help of this NSF grant a new R&D position will be created. The PI will be a role model for entrepreneurial graduate students who are willing to take their work out of the lab and into the marketplace. Another attractive feature is the enzyme-catalyzed “green” manufacturing process. In the longer term the market size can potentially be in the hundreds of millions of dollars as the technology becomes embedded in specific products.