Etude des mécanismes du photoblanchiment de la 5,10,15,20-tetrakis (m-hydroxyphenyl) bactériochlorine, en solution, in vitro et in vivo

Abstract : Photodynamic therapy (PDT) bas been developed as a treatment modality for a number of malignant and non-malignant disorders. PDT treatment is based on the presence of a drug with photosensitising and tumour localizing properties combined with visible light and oxygen. Accurate dosimetry is necessary to ensure complete treatment and to allow for consistent and reproducible patient outcomes. One of the key element which needs to be considered in dosimetry is photobleaching since it decrease the photosensitiser concentration during the treatment. It seems therefore important to understand the photobleaching mechanisms to adapt the photodynamic dose and receive the optimal treatment. The photobleaching quantum yield in solution supplemented with proteins is 5.7 x 10-4 the aggregated forms of the photosensitiser bleach slower than the monomerised forms. Under light exposure the m-THPBC is transformed in m-THPC, the phototransformtion yield is influenced by the aggregation state of the molecule. Some other photoproducts such as di-hydroxy m-THPBC, di-hydroxy m- THPC, dipyrin derivatives were observed. Singlet oxygen was found to be responsible of the photobleaching of both m-THPBC and m-THPC. ln vitro, the m-THPBC LD50 is 0.7 J cm-2, and the photobleaching 3 to 5 times faster than m-THPC. Fluorescence microscopy study exhibits il discrepancy in the photosensitisers localisation, m-THPC is localised is the endop1asmic reticulum and m-THPBC accumulates in mitochondria. ln vivo m- THPBC photobleaching is 4 to 10 times faster than m- THPC, with a good tumour accumulation. Taking as a whole these observations are particularly attractive in terms of therapeutic ratio and selectivity or the treatment and skin photosensitivity.
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Henri-Pierre Lassalle. Etude des mécanismes du photoblanchiment de la 5,10,15,20-tetrakis (m-hydroxyphenyl) bactériochlorine, en solution, in vitro et in vivo. Autre. Université Henri Poincaré - Nancy 1, 2005. Français. ⟨NNT : 2005NAN11309⟩. ⟨tel-01754328⟩

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