Thérapie photodynamique (PDT) dans un modèle in vitro et in vivo de cancer colorectal : utilisation d'un photosensibilisateur nanovectorisé

Abstract : Colorectal cancer (CRC) is one of the most common cancer globally but above all the second leading cause ofdeath for oncological reasons. Despite medical research advances in anti-cancer treatments, many side effectspersist in patients as well as development of resistances to conventional treatments. The development of new anticancertherapeutic strategies is necessary in order to improve care of patients. Photodynamic therapy (PDT) usingphotosensitizers (PS) comes as an innovative therapeutic strategy severely restricting these undesirable sideeffects. PDT has been approved for treatment of some cancers due to the generation of cytotoxic reactive oxygenspecies only with photoactivated PS. However, low physiological solubility and lack of selectivity towards tumorsites are the main limitations of their clinical use. Indeed, targeted drug delivery is a crucial point in cancer therapy.Nanomedicine through the use of nanoparticles improves tumor-targeting because they are able to spontaneouslyaccumulate in solid tumors through an enhanced permeability and retention effect. The purpose of this study wasto prove added value of 5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin-xylan (TPPOH-X) vectorization bysilica nanoparticles (SNPs) in order to enhance anti-cancer efficacy through better tumor-targeting. It has beendemonstrated significant anti-cancer efficacy increase of TPPOH-X SNPs-PDT thanks to cellular uptakeimprovement relative to free TPPOH-PDT in 3 human CRC cell lines. Moreover, it has been characterized thatcell death induced by TPPOH-X SNPs-PDT is conducted via apoptosis and autophagy acts as a resistance pathwayto cell death. Furthermore, in vivo and without toxicity, TPPOH-X SNPs-PDT induce an elevated anti-cancerefficacy through improvement of tumor-targeting compared to free TPPOH-PDT. This study therefore highlightedthe added value of PDT and nanomedicine combination in order to improve future cancer treatments.
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Ludovic Bretin. Thérapie photodynamique (PDT) dans un modèle in vitro et in vivo de cancer colorectal : utilisation d'un photosensibilisateur nanovectorisé. Médecine humaine et pathologie. Université de Limoges, 2019. Français. ⟨NNT : 2019LIMO0052⟩. ⟨tel-02443215⟩

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