Porphyrin synthesis from ALA derivatives for photodynamic therapy: In vitro and in vivo studies
| Autor: | G DiVenosa, Haydée Fukuda, Alcira Batlle, Adriana Casas, Christian Perotti, A. J. MacRobert |
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| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Male
Cancer Research medicine.medical_treatment correlation analysis Photodynamic therapy animal cell undecanoyl 5 aminolevulinic acid purl.org/becyt/ford/1 [https] chemistry.chemical_compound phototoxicity Mice PHOTODYNAMIC THERAPY 0302 clinical medicine Bagg albino mouse drug uptake animal drug determination Heme 0303 health sciences Mice Inbred BALB C Photosensitizing Agents breast tumor article ion exchange chromatography methodology cell line ALA derivatives unclassified drug photochemotherapy bioaccumulation photodynamic therapy Oncology Biochemistry priority journal 030220 oncology & carcinogenesis AMINOLEVULINIC ACID porphyrin experimental neoplasm Porphyrins animal experiment Mammary Neoplasms Animal photosensitizing agent Biology chemistry animal tissue 03 medical and health sciences PDT In vivo medicine purl.org/becyt/ford/1.4 [https] Distribution (pharmacology) Animals Experimental Therapeutics controlled study mouse 030304 developmental biology porphyrin metabolism nonhuman hexyl 5 aminolevulinic acid animal model explant ALA Aminolevulinic Acid Porphyrin In vitro drug efficacy ALA DERIVATIVES Photochemotherapy Cell culture drug derivative 2 (hydroxymethyl)tetrahydropyranyl 5 aminolevulinic acid biosynthesis Explant culture |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Br. J. Cancer 2004;90(8):1660-1665 Biblioteca Digital (UBA-FCEN) Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales instacron:UBA-FCEN British Journal of Cancer |
| Popis: | The aim of this work was to test in vitro and in vivo the efficacy of the derivatives of 5-aminolevulinic acid (ALA): hexyl-ALA (He-ALA), undecanoyl-ALA and R,S-2-(hydroximethyl)tetrahydropyranyl-ALA (THP-ALA) as pro-photosensitising agents. The compounds were assayed in a cell line derived from a murine mammary tumour, in tumour explants and after injection of the cells into mice. In vitro, undecanoyl-ALA and THP-ALA did not improve ALA efficacy in terms of porphyrin synthesis. On the other hand, half of the amount of ALA is required to obtain the same plateau amount of photosensitiser from He-ALA. However, this plateau value cannot be surpassed in spite of the four-times higher accumulation of ALA/He-ALA from the ALA derivative. This shows that He-ALA conversion to porphyrins but not He-ALA entry to the cells is limiting. Employing ionic exchange chromatography, we found that 80% of total uptake was He-ALA whereas only 20% was ALA. This suggests that the esterases, probably themselves regulated by the heme pathway, are limiting the conversion of ALA derivatives into porphyrins. A similar situation occurs with THP-ALA. Tumour explant porphyrin results correlate well with cell line data. However, i.p. injection of ALA derivatives to mice resulted in a lower porphyrin concentration in the tumour when compared to the administration of equimolar amounts of ALA, indicating that there should be retention of ALA derivatives either within the blood vessels in the initial phase of distribution and/or within the capillaries of the tumour. © 2004 Cancer Research UK. Fil: Perotti, C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina Fil: Fukuda, Haydee. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina Fil: Di Venosa, Gabriela Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina Fil: MacRobert, A.J.. No especifíca; Fil: Batlle, Alcira María del C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina Fil: Casas, Adriana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina |
| Databáze: | OpenAIRE |
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