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Vectorisation cellulaire et adressage mitochondrial de photosensibilisateurs par des nanoparticules formées de xylane de bois de feuillus : nouvelle voie de valorisation d'hémicellulose pour une application en PDT

Abstract : The most used photosensitizers in photodynamic therapy (PDT) are porphyrins and their derivatives. However, these compounds often suffer from low solubility in physiological media and a lack of selectivity towards cancer cells which limits their clinical uses. One of the most promising strategies to overcome these problems is the use of nanoparticles as a vector of photosensitizers (PS). In this context, we have developed xylan-based nanoparticles for targeted delivery of porphyrins. Two types of nanoparticles have been studied: core-shell hybrid nanoparticles, and organic nanoparticles. In a first study, xylan-porphyrins were used to coat silica nanoparticles (SNPs). Indeed, the presence of glucuronic acid groups on xylan allows the formation of ionic bonds on the surface of the SNPs made cationic by ammonium salts. The biological evaluation of these nano-objects has shown that the combination of porphyrins with nanoparticles increases their photodynamic activity. In addition, mitochondrial targeting with triphenylphosphonium (TPP) increases significantly therapeutic efficacy of this PS. In a second approach, we have demonstrated that xylans-porphyrins can form nanoparticles fully organic by self-assembly in. Different nanoobjects with variable degree of substitution in porphyrins have been obtained and characterized. In parallel, 100% natural nanoparticles from chestnut xylan and natural chlorine, pheophorbide a were obtained and characterized. The biological evaluation of these nanoparticles is in progress and preliminary results are very encouraging
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Soukaina Bouramtane. Vectorisation cellulaire et adressage mitochondrial de photosensibilisateurs par des nanoparticules formées de xylane de bois de feuillus : nouvelle voie de valorisation d'hémicellulose pour une application en PDT. Chimie organique. Université de Limoges, 2019. Français. ⟨NNT : 2019LIMO0094⟩. ⟨tel-02468447⟩

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