We propose to develop new fullerene-based photosensitizers (PS) for topical photodynamic therapy of pre-malignant lesions of the oral cavity and pharynx. Photodynamic therapy (PDT) is a non-invasive procedure that uses a non-toxic photosensitizer and visible light to generate reactive oxygen species that kill biological cells. An advantage of PDT is its high level of selectivity, achieved through PS that selectively target specific cell or tissue types, the topical application of the PS to diseased tissue only, and the ability to control the illumination area. In addition, PDT can usually be performed on an out-patient basis. Currently, there are no photosensitizers approved for use with oral lesions. The potential advantages of our approach are: 1) Illumination can be carried out immediately after the topical application of the PS (there is no lengthy incubation period as required with other competing PS), 2) there is no need for laser light as with other PS, regular visible light is sufficient, 3) there is no skin and eye photosensitivity that many patients face after treatment. By developing a novel PS for the treatment of pre-malignant lesions, we will bring a welcome addition to the growing arsenal of cancer and pre-cancer treatments with superior ease of use, patient comfort, and cosmetic outcome. ? ? ?