Analisi struttura- funzione di coloranti polimetinici cianinici per la terapia fotodinamica.

Photodynamic therapy (PDT) is an emerging, minimally invasive therapeutic modality approved by the U.S Food and Drug Administration for the treatment of several conditions, such as different types of cancer. This approach is based on the local administration and retention of a photosensitizer pro-drug in tumor tissue followed by irradiation with infrared or visible light of a wavelength which coincides with the absorption spectrum of the photosensitizer agent. Following the absorption of a photon, the photosensitizer switches from its ground singlet state to the excited singlet state and undergo to a triplet state that reacts easily with molecular oxygen, generating free radicals and singlet oxygen species. The generated oxidative stress is very short lived and causes death in the irradiated cells. This therapy has a direct impact locally but may also induce a more delayed systemic immune response. Different types of molecules with high photo-activity have been developed and used in PDT. In particular, polymethine dyes (PMDs) have been shown to be a successful singlet oxygen (1O2) generators and photosensitizers in PDT studies. My thesis project focus on the study of the relationship between the structure and the photo-activity of cyanines PMDs; in particular I analyzed the role of the heavy atoms presence and nature in Cyanine C4 both in terms of cytotoxicity as well as photoactivity. In addition, a Design of Experiment (DoE) has been used as an approach, to find the optimal condition of the process, to reduce and minimize the number of the experiments and obtain accurate and precise results. Different empiric models using experimental data were developed for each PMDs, through the employment of software MODDE pro. Finally, the various models obtained were compared in order to identify the best PMDs candidate.