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A synergistic combination therapy of photodynamic therapy and chemotherapy for breast cancer.

Youngjae You Ph.D.

Principal Investigator

Agency: Department of Defense BCRP Idea Expansion Award

Abstract

Unfortunately, patients experience sytemic (throughout the boy) side effects from chemotherapy even when their breast tumors are localized (restricted to one area), because cancer-treating drugs are administered systemically. These systemic side effects produce enormous physical and mental burdens to patients, as well as limit the amount of a chemotherapy drug that can be given. Thus, better strategies for localized breast cancer chemotherapy must be developed to minimize the side effects and provide more effective treatment. In addition, triple-negative breat cancers cannot be treated with hormonal therapy or targeted therapy. We developed an innovative strategy in which anticancer drugs can be locally released from prodrugs (or inactive chemotherapy drugs) in a controlled manner. The unique feature of our approach is the active control of drug release using near infra-red light via a fiber optic cable. This approach minimizes the body's exposure to chemotherapeutic drugs, because it allows the targeted delivery of drugs to the tumor site, thus reducing systemic side effects for patients as much as possible. With funding from our BCRP Idea Award, we were the first to successfully demonstrate this strategy as a method of treating tumors tumores in a mouse model.

The use of near infrared light offers a number of advantages. Near infrared light is not toxic, unlike ultraviolet light and high-energy radiation, such as X-rays or gamma rays. It can also reach up to a few centimeters (approx. one inch) inside body tissues, while ultraviolet and short visible light cannot do so. Near infrared can be presented by a small and portable source, and can be delivered va a fiber optic cable. Unfortunately, near infrared light has not been successfully used for therapeutic applications because of its inability to break chemical bonds that keep an inactivated drug from working. Once these bonds aare broken, the drug becomes active and kills tumor cells. Recently, we discovered a groundbreaking way to break these bonds using infrared light, thus allowing us to now be able to use near infrared light break the bonds that keep prodrugs inactive and release the active drug at the tumor site.

Our proposal applies our novel strategy to the treatment of triple-negative breast cancers. We will create a near infrared-activatable prodrug with a component that is targeted to this type of breast tumor (a tumor-targeting ligand). This means that the prodrug specifically to breast tumor sites. Then we will use near-infrared light to break the chemical bonds and release the anticancer drug. For our project, we will prepare prodrugs from the clinically approved anticance drug paclitax. If our strategy is successful, it will be a significant advancement toward an effective and innovative treatment option that has minimal systemic side effects for the localized and inoperable advanced triple-negative breast cancers.