title: Hydroxypyridinone and 5-Aminolaevulinic Acid Conjugates for Photodynamic Therapy.
abstract: Photodynamic therapy (PDT) is a promising treatment strategy for malignant and nonmalignant lesions. 5-Aminolaevulinic acid (ALA) is used as a precursor of the photosensitizer, protoporphyrin IX (PpIX), in dermatology and urology. However, the effectiveness of ALA-PDT is limited by the relatively poor bioavailability of ALA and rapid conversion of PpIX to haem. The main goal of this study was to prepare and investigate a library of single conjugates designed to coadminister the bioactive agents ALA and hydroxypyridinone (HPO) iron chelators. A significant increase in intracellular PpIX levels was observed in all cell lines tested when compared to the administration of ALA alone. The higher PpIX levels observed using the conjugates correlated well with the observed phototoxicity following exposure of cells to light. Passive diffusion appears to be the main mechanism for the majority of ALA-HPOs investigated. This study demonstrates that ALA-HPOs significantly enhance phototherapeutic metabolite formation and phototoxicity.
authors.affiliation: School of Biological Sciences, University of Essex , Colchester CO4 3SQ, U.K.|Division of Surgery and Interventional Science, University College London , Charles Bell House, 67-73 Riding House Street, London W1W 7JE, U.K.
authors.forename: Sinan
authors.initials: S
authors.lastname: Battah
authors.affiliation: Division of Pharmaceutical Sciences, King's College London , 150 Stamford Street, London SE1 9NH, U.K.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hider
authors.affiliation: Division of Surgery and Interventional Science, University College London , Charles Bell House, 67-73 Riding House Street, London W1W 7JE, U.K.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: MacRobert
authors.affiliation: School of Biological Sciences, University of Essex , Colchester CO4 3SQ, U.K.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Dobbin
authors.affiliation: School of Food Science and Biotechnology, Zhejiang Gongshang University , Hangzhou, Zhejiang 310018, P. R. China.
authors.forename: Tao
authors.identifier: 0000-0003-4510-3639
authors.initials: T
authors.lastname: Zhou
mesh_terms: D000622:Aminolevulinic Acid / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D010778:Photochemotherapy; D011725:Pyridines / Q000737:chemistry*
chemical_list: D011725:Pyridines; C014047:hydroxypyridines; D000622:Aminolevulinic Acid