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Physico-chimie de méso-tétraphénylporphyrines glycoconjuguées pour la photothérapie dynamique : vers une meilleure compréhension de la distribution plasmatique et de la localisation subcellulaire ?

Abstract : Photodynamic Therapy (PDT) is based on the destruction of a tumor tissue through a combinationof administration of a photosensitizer and exposure to visible light. This work includes : i) a study of ionization and hydrophobicity of a series of candidate sensitizers, glycoconjugated mesotetraphenylporphyrins (TPP), ii) an evaluation of the impact of those two physico-chemicalproperties on sensitizer's plasma distribution and subcellular localization. Protonation of tetrapyrrolic nitrogens has been studied by electronic spectroscopy combined with chemometric analysis whereas hydrophobicity has been evaluated by high-performance liquid chromatography. The effect of substitution modalities (position, number and nature of pendantgroups) on both physico-chemical properties has been evidenced.In human plasma, glycoconjugated TPPs mainly bind to high density lipoproteins. Hydrophobicity accounts for differences in affinities towards lipoproteins, but not towards albumin. Subcellular localization studies, combining computational and experimental approaches, led to formulate some assumptions explaining localization of TPP(pODEGOαManOH)3 in endoplasmic reticulum,assumptions centered on a major role of sensitizer's hydrophobicity. At the end of this work, before trying to use our conclusions for the design of new sensitizers, it remains necessary to better explore the effect of plasma distribution and subcellular localization on sensitizer's photo-efficiency.
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Benoît Chauvin. Physico-chimie de méso-tétraphénylporphyrines glycoconjuguées pour la photothérapie dynamique : vers une meilleure compréhension de la distribution plasmatique et de la localisation subcellulaire ?. Médecine humaine et pathologie. Université Paris Sud - Paris XI, 2011. Français. ⟨NNT : 2011PA114824⟩. ⟨tel-00660396⟩

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