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

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, Adriana Gabriela, Fukuda, Haydeé, Di Venosa, Gabriela Mariana, Batlle, Alcira María del Carmen
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:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00070920_v85_n2_p279_Casas http://hdl.handle.net/20.500.12110/paper_00070920_v85_n2_p279_Casas
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00070920_v85_n2_p279_Casas
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spelling	paper:paper_00070920_v85_n2_p279_Casas2023-06-08T14:31:33Z Photosensitization and mechanism of cytotoxicity induced by the use of ALA derivatives in photodynamic therapy Casas, Adriana Gabriela Fukuda, Haydeé Di Venosa, Gabriela Mariana Batlle, Alcira María del Carmen 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 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. 2001 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00070920_v85_n2_p279_Casas http://hdl.handle.net/20.500.12110/paper_00070920_v85_n2_p279_Casas
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (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, Adriana Gabriela Fukuda, Haydeé Di Venosa, Gabriela Mariana Batlle, Alcira María del Carmen 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.
author	Casas, Adriana Gabriela Fukuda, Haydeé Di Venosa, Gabriela Mariana Batlle, Alcira María del Carmen
author_facet	Casas, Adriana Gabriela Fukuda, Haydeé Di Venosa, Gabriela Mariana Batlle, Alcira María del Carmen
author_sort	Casas, Adriana Gabriela
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	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00070920_v85_n2_p279_Casas http://hdl.handle.net/20.500.12110/paper_00070920_v85_n2_p279_Casas
work_keys_str_mv	AT casasadrianagabriela photosensitizationandmechanismofcytotoxicityinducedbytheuseofaladerivativesinphotodynamictherapy AT fukudahaydee photosensitizationandmechanismofcytotoxicityinducedbytheuseofaladerivativesinphotodynamictherapy AT divenosagabrielamariana photosensitizationandmechanismofcytotoxicityinducedbytheuseofaladerivativesinphotodynamictherapy AT batllealciramariadelcarmen photosensitizationandmechanismofcytotoxicityinducedbytheuseofaladerivativesinphotodynamictherapy
_version_	1768544757771927552

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

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