? According to the National Psoriasis Foundation, psoriasis is one of the leading causes of skin disease in the United States, affecting 5.5 million Americans and costing $2-$3 billion annually. An exciting, nanotechnology approach will be taken to develop a next generation photosensitizer to be used in photodynamic therapy (PDT) for the disease. Biochemically modified TiO2 nanoparticles will be linked to select targeting moieties to make an activated T cell specific semiconductor nanoparticle, which displays exceptional electronic and photocatalytic reactivities. Incorporation of an """"""""electronic bridge"""""""" to markers on the T cell surface should allow the redox potential of these molecules to be """"""""focused"""""""" and delivered to the cell. Thus, the robustness and reactivities of """"""""hard"""""""" (inorganic) matter will be combined with the extraordinary selectivity of """"""""soft"""""""" (biological) matter to effect specific changes at the cellular level and ultimately impact the pathogenesis of psoriasis. ? ? This approach, which does not preclude the use of other therapies, is expected to result in high reactivity and selectivity compared to currently treatments. The particles are designed to target specific cellular mediators of the disease and be activated by visible wavelengths of light. It is anticipated that this approach will have an improved safety and convenience profile when compared with current photodynamic or traditional therapies, which are often accompanied by serious side effects, require UV light, or are injected under the skin. In this proposal, functionalized nanoparticles will be constructed, characterized, and tested for chemical and biological activity against targeted T cells to demonstrate proof of concept. Basic optimization studies will then enhance the particles' selective cytotoxic effects in anticipation of their development as the central component of a novel, highly effective, safe and convenient therapy for psoriasis. ? ?
