Étude par spectrométrie de masse des photoréactions laser de sensibilisants colorés utilisés en thérapie photodynamique (PDT)

Abstract : Photodynamic therapy is based on light activation localized in tumors. Such phototherapeutic compounds have no toxicity when they are not under light. However, under laser irradiation, photosensitizers produce specific chemical species that lead to tumor elimination. 5,10,15,20-méso(tetrahydroxyphenyl) chlorin (m-THPC) is compound that shows the greatest photodynamic activity. Many studies dealing with this compound under various media or in clinical conditions have been carried out. However the photodynamic mechanisms are not yet explained. During this thesis, we investigated the m-THPC photodynamic processes by different physicochemistry methods : spectrophotometry (UV/Visible and fluorescence) and mass spectrometry (MALDI/FTICRMS). Moreover, we also studied the 5,10,15,20-méso(tetrahydroxyphenyl) porphyrin (m-THPP) and the 5,10,15,20-méso(tetrahydroxyphenyl) bactériochlorine (m-THPBC) behaviors. We determined firstly the mass fingerprints of the three considered photosesitizers. Then, secondly, we considered the m-THPC photodegradation behavior in ethanol, which lead to the formation of dihydroxy-m-THPC compounds. The study of m-THPC and m-THPBC behavior in ethanol-water or in physiological media with or without preoteins, allowed us to highlight the m-THPP formation through a dehydrogenation process. Finally, a preliminary study of m-THPC cellular medium (blood platelets), validated our direct characterization of this photosensitizer by MALDI/FTICRMS. In biological media, the dehydrogenation process of the m-THPC that gives m-THPP was also absolved
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Marc Angotti. Étude par spectrométrie de masse des photoréactions laser de sensibilisants colorés utilisés en thérapie photodynamique (PDT). Chimie-Physique [physics.chem-ph]. Université Paul Verlaine - Metz, 2001. Français. ⟨NNT : 2001METZ024S⟩. ⟨tel-01775439⟩

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