Optimization of proteolytically induced photosensitizers for fluorescence imaging and Photodynamic Therapy

Diplôme Thèse Optimization of proteolytically induced photosensitizers for fluorescence imaging and Photodynamic Therapy eng 2014-09-26 author Sekkat Nawal 584320 director Lange Norbert 135650 10.13097/archive-ouverte/unige:47392 urn:nbn:ch:unige-473928 Sc. 4719 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. Photodetection Photodynamic Therapy Protease Sensitive Photosensitizer Prodrugs Near-infrared Photosensitizers Phthalocyanines Pheophorbide a Molecular Beacons Protease Sensitive Polymeric Prodrugs Regioselectively Addressable Functionalized Templates Protease Sensitive Prodrugs Dewey 615 31 Section des sciences pharmaceutiques 17 false 883 Technologie pharmaceutique 70ce6a2a-a6e0-41a1-bd17-68fbe8db2f92 Thesis Public These Finale Nawal SEKKAT.pdf 4158015 application/pdf openAccess Faculté des sciences / Section des sciences pharmaceutiques

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Sekkat, Nawal