Novel Nanostructures for Topical Photodynamic Therapy

DESCRIPTION (provided by applicant): Fullerenes are a class of closed-cage nanomaterials comprised exclusively of carbon atoms. A great deal of attention has been focused on developing medical uses of these unique molecules. This proposal concerns the development of fullerenes in antimicrobial photodynamic therapy, a non-invasive procedure that combines a non-toxic photosensitizer with harmless visible light to kill microbial cells. An advantage of photodynamic therapy is its high level of selectivity. This is achieved by using photosensitizers that selectively target specific cell types and by controlling the area that is illuminated. In the Phase I study, a number of fullerene-based photosensitizers with highly desirable properties were synthesized and tested. The PS inactivated a broad spectrum of microbes (6 log reduction of gram positive bacteria, gram negative bacteria and fungi). The Phase I results are particularly encouraging because the fullerene photosensitizers were effective at low concentrations and needed only low levels of illumination. In addition, under conditions where bacterial cells were killed, mammalian cells were unharmed. Tests also showed that the fullerene photosensitizers performed substantially better than an antimicrobial photosensitizer commonly used in clinical practice. In the Phase II study, an understanding of the relationship between the nanoscale properties of fullerenes and their ability to selectively photoinactivate microorganisms will be developed, leading to the commercial development of treatments for localized bacterial and fungal infections. In addition, the PS will be tested for the mediation of topical PDT in mouse models of infected wounds and burns using bioluminescent bacteria and low-light imaging to follow infection progress in real time. Antimicrobial photodynamic therapy can serve as a new technique to combat pathogenic bacteria that have developed antibiotic resistance. Wound infections affect millions of Americans each year. With ever increasing antibiotic resistance, antimicrobials are sought for treatment of localized infections (bacterial and fungal) with applications in dermatology, dentistry, and ophthalmology. A global market of $3 billion dollars is projected, representing a significant opportunity for commercialization.