Caractérisation par spectrométrie de masse d'extraits de millepertuis potentiellement utilisables en photodiagnostic et photothérapie des cancers : étude de leurs propriétés photochimiques en solution et en milieu cellulaire

Abstract : Photodynamic therapy (PDT) combines light with a drug called photosensitizing agent, which preferentially accumulates in cancerous cells. Irradiated with visible light, this photosensitizing agent generates singlet oxygen (1O2) and radicals that demonstrate cell toxicity. Fluorescence of this drug also allows diagnosing neoplasic lesions: this is photodynamic diagnosis (PDD).St John?s Wort extracts, mainly known for their antidepressant activity, also contain photoactive compounds, including hypericin which has been extensively studied for PDT and PDD. However, producing this molecule in large amounts is expensive and its use is restricted by a poor solubility in physiological medium. In this context, the present study deals with determining in what extent St John?s Wort extracts could be useful for PDT and PDD. Flowers that were used in this work were firstly in situ-analyzed by mass spectrometry in order to characterized photoactive compounds at the level of structures involved in their biosynthesis. These compounds were then extracted by organic solvent and the resulting mixture subjected to singlet oxygen production measurements under laser illumination. Qualitative analysis of the extracts was then performed either by Laser Desorption/Ionization or Electrospray Ionization coupled with Mass Spectrometry (TOF and FTICR). Finally, their behavior in cellular medium (bladder cancer) was investigated in terms of dark cytotoxicity, intracellular accumulation of photoactive compounds, phototoxicity and characterization of compounds absorbed by cells
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Audrey Hecka. Caractérisation par spectrométrie de masse d'extraits de millepertuis potentiellement utilisables en photodiagnostic et photothérapie des cancers : étude de leurs propriétés photochimiques en solution et en milieu cellulaire. Autre. Université Paul Verlaine - Metz, 2009. Français. ⟨NNT : 2009METZ052S⟩. ⟨tel-01752925⟩

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