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Title

Optimization of proteolytically induced photosensitizers for fluorescence imaging and Photodynamic Therapy

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Defense Thèse de doctorat : Univ. Genève, 2014 - Sc. 4719 - 2014/09/26
Abstract The scope of this thesis is to investigate and improve efficiency and selectivity of Photodetection and Photodynamic Therapy using near-infrared photosensitizers (PS) and protease sensitive photosensitizer prodrugs (PSPP) for PS-controlled, versatile and modulable delivery to diseased tissues. Photosensitizers comprising of phthalocyanines, and pheophorbide-a and PSPP Constructs i.e. Molecular Beacons, Protease Sensitive Polymeric Prodrugs (PPP) and Regioselectively Addressable Functionalized Templates (RAFT) Protease Sensitive Prodrugs were successfully synthesized and evaluated both in vitro and in vivo. 50% of prostate cancer (PC-3) cell death was achieved for PS-doses as low as 100nM for a light dose of 10J/cm2 using RAFT prodrugs. Complete tumor eradication was observed on 3 out of 7 mice bearing tumor xenografts using PPP. The PSPP therefore exhibited very promising potential for detection, imaging and treatment of the tumors. Having established the modulability of the prodrug approaches, new therapeutical applications could be envisaged in diseases associated with proteases up-regulated levels.
Keywords PhotodetectionPhotodynamic TherapyProtease Sensitive Photosensitizer ProdrugsNear-infrared PhotosensitizersPhthalocyaninesPheophorbide aMolecular BeaconsProtease Sensitive Polymeric ProdrugsRegioselectively Addressable Functionalized Templates Protease Sensitive Prodrugs
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URN: urn:nbn:ch:unige-473928
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Research group Technologie pharmaceutique
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SEKKAT, Nawal. Optimization of proteolytically induced photosensitizers for fluorescence imaging and Photodynamic Therapy. Université de Genève. Thèse, 2014. https://archive-ouverte.unige.ch/unige:47392

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Deposited on : 2015-03-02

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