Photodynamic therapy has gained acceptance as a technique for cancer treatment in recent years. It utilizes a photosensitizer to treat the target tissue locally upon the irradiation with light of appropriate wavelengths. It is generally accepted that the mechanism of photodynamic therapy is based on the interaction between the excited photosensitizer and surrounding molecules, generating reactive oxygen species, which will then cause damage to biological substrates and ultimately cell death. Yet, photodynamic therapy suffers from major drawbacks and limitations, and needs improvement in its efficacy to reach the full potential. The objective of this project is to design and develop infrared excitable photosensitizers for targeted photodynamic therapy, based on photon upconverting nanoparticles. It is hypothesized that photosensitizers of the design discussed in the proposal will (1) have deeper tissue penetration; (2) be highly specific to the target; and (3) be versatile, with regard to the types of photoactivated molecules included and of targeting agents attached. This proposal will focus on the design, engineering and in vitro biological tests of these nanoparticle-based photosensitizers. This project will be the first study following such strategy. The development of the proposed nanoparticle-based photosensitizers would address the tissue penetration depth issue in photodynamic therapy, and make it more feasible to apply for treatments of deep-tissue cancers.
With the advancement of photodynamic therapy drug development, it will become feasible to use photodynamic therapy for cancer treatments, especially when in combination with adjuvant therapies. The issues addressed could set the stage for the development of next generation photodynamic therapy drugs, and the improvement of photodynamic therapy for cancer treatment. Results of the research will be disseminated through contributions in peer-reviewed journals, and conference contributions. Education will be an integral part of the proposed research by including graduate, undergraduate students and local high school student(s) in the projects. Students of underrepresented groups will be recruited to participate in the research program.
