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New strategies for the induction of endogenous porphyrins in eurcaryotic and procaryotic cells

Defense Thèse de doctorat : Univ. Genève, 2012 - Sc. 4415 - 2012/04/20
Abstract The present thesis presents new strategies to generate endogenous porphyrins from exogenously provided compounds for fluorescence photodetection (PD) and photodynamic therapy (PDT). One method is to administer the heme precursor 5-aminolevulinic acid (5-ALA), which leads to the accumulation of fluorescent intermediates of the heme cycle, notably protoporphyrin IX (PPIX).The hexyl ester of 5-ALA (HAL) has gained marketing authorization for the detection of bladder cancer from the european, australian and american regulatory offices. However, its impact for other indications such as interstitial tumors is relatively small due limited systemic bioavailability. Aiming at reducing the systemic toxicity and improving the circulation half-life of the compound, the first part of the thesis focuses on the encapsulation of HAL into polymeric nanoparticles. The second part of the thesis relates to the discovery, characterization and preliminary exploitation of a PPIX generating mechanism from heme in E.coli.
Keywords 5-aminolevulinic acidHexaminolevulinic acidProtoporphyrin ixPhotodynamic therapyFluorescence photodetectionE. coliHemeNanoparticlesPolylactic acidDrug delivery.
URN: urn:nbn:ch:unige-219862
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HEUCK, Gesine. New strategies for the induction of endogenous porphyrins in eurcaryotic and procaryotic cells. Université de Genève. Thèse, 2012. doi: 10.13097/archive-ouverte/unige:21986 https://archive-ouverte.unige.ch/unige:21986

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Deposited on : 2012-08-10

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