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Pour une amélioration de la thérapie photodynamique appliquée à la cancérologie : potentialités des dendrimères poly(amidoamine) et des Quantum Dots CdTe adressés par l'acide folique

Abstract : Photodynamic therapy (PDT) efficiency is confronted to various barriers, such as photosensitizers (PSs) which are not optimized to the therapeutic window and endure photobleaching during treatment, moreover their organic nature can also lead to solubility problems for biological uses. Usual PSs show also a lack of selectivity toward tumor tissues to treat. In order to improve PDT treatment, three approaches were studied: delivery, targeting and use of a new class of photosensitizing agents. Synthesis of PS/delivery vehicle structure enabled to developed hydrophilic structure able to deliver hydrophobic PSs. Porphyrins were linked to dissymmetric polyamidoamine dendrimers. Conservation of the photophysical properties of PSs after linkage to the dendrimer was then highlighted. Due to the modularity of their photophysical properties and their capacity to resist to photobleaching, hydrodispersable Quantum dots (QDs) were synthesized to match the therapeutic window of PDT. In vitro studies of these QDs linked to folic acid showed their ability to induce a photodynamic activity. We used an experimental design approach to distinguish the impact of each experimental factor on the photodynamic activity of these QD-folic acid conjugates. We showed in particular an increase of the selectivity of the folic acid-linked QDs towards cell line overexpressing the folate receptor
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Vincent Morosini. Pour une amélioration de la thérapie photodynamique appliquée à la cancérologie : potentialités des dendrimères poly(amidoamine) et des Quantum Dots CdTe adressés par l'acide folique. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2010. Français. ⟨NNT : 2010NAN10124⟩. ⟨tel-01746383⟩

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