Photosensitization and mechanism of cytotoxicity induced by the use of ALA derivatives in photodynamic therapy
| Autor: | Haydée Fukuda, Alcira Batlle, Adriana Casas, G. Di Venosa |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cancer Research
medicine.medical_treatment Apoptosis Photodynamic therapy animal cell Pharmacology aminolevulinic acid phototoxicity Mice chemistry.chemical_compound Tumor Cells Cultured Photosensitizer Cytotoxicity aminolevulinic acid hexyl ester Photosensitizing Agents Protoporphyrin IX photosensitization apoptosis article Regular Article Photosensitizing Agent ALA derivatives aminolevulinic acid methyl ester unclassified drug cell death photodynamic therapy priority journal Oncology protoporphyrin cytotoxicity drug diffusion Phototoxicity Cell Survival Biology PDT medicine Animals Viability assay cell viability mouse nonhuman ALA Aminolevulinic Acid Microscopy Fluorescence Photochemotherapy chemistry concentration response Immunology |
| Zdroj: | Br. J. Cancer 2001;85(2):279-284 Biblioteca Digital (UBA-FCEN) Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales instacron:UBA-FCEN British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | The use of more lipophilic derivatives of 5-aminolevulinic acid (ALA) is expected to have better diffusing properties, and after conversion into the parent ALA, to reach a higher protoporphyrin IX (PPIX) formation rate, thus improving the efficacy of topical photodynamic therapy (PDT). Here we have analysed the behaviour of 3 ALA derivatives (ALA methyl-ester, hexyl ester and a 2-sided derivative) regarding PPIX formation, efficiency in photosensitizing cells and mechanism of cellular death. The maximum amount of porphyrins synthesized from 0.6 mM ALA was 47 ± 8 ng/105 cells. The same amount was formed by a concentration 60-fold lower of hexyl-ALA and 2-fold higher of methyl-ALA. The 2-sided derivative failed to produce PPIX accumulation. Applying a 0.6 J cm-2 light dose, cell viability decreased to 50%. With the 1.5 J cm-2 light dose, less than 20% of the cells survive, and higher light doses produced nearly total cell killing. Comparing the PPIX production and the induced phototoxicity, the more the amount of porphyrins, the greater the cellular killing, and PPIX formed from either ALA or ALA-esters equally sensitize the cells to photoinactivation. ALA-PDT treated cells exhibited features of apoptosis, independently on the pro-photosensitizer employed. ALA-PDT can be improved with the use of ALA derivatives, reducing the amount of ALA necessary to induce efficient photosensitization. © 2001 Cancer Research Campaign. Fil:Casas, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fukuda, H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Di Venosa, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Batlle, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. |
| Databáze: | OpenAIRE |
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