Photosensitization and mechanism of cytotoxicity induced by the use of ALA derivatives in photodynamic therapy

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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...

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Autores principales: Casas, A., Fukuda, H., Di Venosa, G., Batlle, A.
Formato: Artículo publishedVersion
Publicado: 2001
Materias:
ALA
ALA derivatives
Aminolevulinic acid
Apoptosis
PDT
Photodynamic therapy
aminolevulinic acid
aminolevulinic acid hexyl ester
aminolevulinic acid methyl ester
protoporphyrin
unclassified drug
animal cell
apoptosis
article
cell death
cell viability
concentration response
cytotoxicity
drug diffusion
mouse
nonhuman
photodynamic therapy
photosensitization
phototoxicity
priority journal
Aminolevulinic Acid
Animals
Cell Survival
Mice
Microscopy, Fluorescence
Photochemotherapy
Photosensitizing Agents
Tumor Cells, Cultured
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00070920_v85_n2_p279_Casas
https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00070920_v85_n2_p279_Casas_oai
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Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
id I28-R145-paper_00070920_v85_n2_p279_Casas_oai
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spelling I28-R145-paper_00070920_v85_n2_p279_Casas_oai2024-08-16 Casas, A. Fukuda, H. Di Venosa, G. Batlle, A. 2001 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. application/pdf http://hdl.handle.net/20.500.12110/paper_00070920_v85_n2_p279_Casas info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar Br. J. Cancer 2001;85(2):279-284 ALA ALA derivatives Aminolevulinic acid Apoptosis PDT Photodynamic therapy aminolevulinic acid aminolevulinic acid hexyl ester aminolevulinic acid methyl ester protoporphyrin unclassified drug animal cell apoptosis article cell death cell viability concentration response cytotoxicity drug diffusion mouse nonhuman photodynamic therapy photosensitization phototoxicity priority journal Aminolevulinic Acid Animals Apoptosis Cell Survival Mice Microscopy, Fluorescence Photochemotherapy Photosensitizing Agents Tumor Cells, Cultured Photosensitization and mechanism of cytotoxicity induced by the use of ALA derivatives in photodynamic therapy info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00070920_v85_n2_p279_Casas_oai
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
topic ALA
ALA derivatives
Aminolevulinic acid
Apoptosis
PDT
Photodynamic therapy
aminolevulinic acid
aminolevulinic acid hexyl ester
aminolevulinic acid methyl ester
protoporphyrin
unclassified drug
animal cell
apoptosis
article
cell death
cell viability
concentration response
cytotoxicity
drug diffusion
mouse
nonhuman
photodynamic therapy
photosensitization
phototoxicity
priority journal
Aminolevulinic Acid
Animals
Apoptosis
Cell Survival
Mice
Microscopy, Fluorescence
Photochemotherapy
Photosensitizing Agents
Tumor Cells, Cultured
spellingShingle ALA
ALA derivatives
Aminolevulinic acid
Apoptosis
PDT
Photodynamic therapy
aminolevulinic acid
aminolevulinic acid hexyl ester
aminolevulinic acid methyl ester
protoporphyrin
unclassified drug
animal cell
apoptosis
article
cell death
cell viability
concentration response
cytotoxicity
drug diffusion
mouse
nonhuman
photodynamic therapy
photosensitization
phototoxicity
priority journal
Aminolevulinic Acid
Animals
Apoptosis
Cell Survival
Mice
Microscopy, Fluorescence
Photochemotherapy
Photosensitizing Agents
Tumor Cells, Cultured
Casas, A.
Fukuda, H.
Di Venosa, G.
Batlle, A.
Photosensitization and mechanism of cytotoxicity induced by the use of ALA derivatives in photodynamic therapy
topic_facet ALA
ALA derivatives
Aminolevulinic acid
Apoptosis
PDT
Photodynamic therapy
aminolevulinic acid
aminolevulinic acid hexyl ester
aminolevulinic acid methyl ester
protoporphyrin
unclassified drug
animal cell
apoptosis
article
cell death
cell viability
concentration response
cytotoxicity
drug diffusion
mouse
nonhuman
photodynamic therapy
photosensitization
phototoxicity
priority journal
Aminolevulinic Acid
Animals
Apoptosis
Cell Survival
Mice
Microscopy, Fluorescence
Photochemotherapy
Photosensitizing Agents
Tumor Cells, Cultured
description 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.
format Artículo
Artículo
publishedVersion
author Casas, A.
Fukuda, H.
Di Venosa, G.
Batlle, A.
author_facet Casas, A.
Fukuda, H.
Di Venosa, G.
Batlle, A.
author_sort Casas, A.
title Photosensitization and mechanism of cytotoxicity induced by the use of ALA derivatives in photodynamic therapy
title_short Photosensitization and mechanism of cytotoxicity induced by the use of ALA derivatives in photodynamic therapy
title_full Photosensitization and mechanism of cytotoxicity induced by the use of ALA derivatives in photodynamic therapy
title_fullStr Photosensitization and mechanism of cytotoxicity induced by the use of ALA derivatives in photodynamic therapy
title_full_unstemmed Photosensitization and mechanism of cytotoxicity induced by the use of ALA derivatives in photodynamic therapy
title_sort photosensitization and mechanism of cytotoxicity induced by the use of ala derivatives in photodynamic therapy
publishDate 2001
url http://hdl.handle.net/20.500.12110/paper_00070920_v85_n2_p279_Casas
https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00070920_v85_n2_p279_Casas_oai
work_keys_str_mv AT casasa photosensitizationandmechanismofcytotoxicityinducedbytheuseofaladerivativesinphotodynamictherapy
AT fukudah photosensitizationandmechanismofcytotoxicityinducedbytheuseofaladerivativesinphotodynamictherapy
AT divenosag photosensitizationandmechanismofcytotoxicityinducedbytheuseofaladerivativesinphotodynamictherapy
AT batllea photosensitizationandmechanismofcytotoxicityinducedbytheuseofaladerivativesinphotodynamictherapy
_version_ 1809357051962327040

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