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Artículo

Photodynamic therapy of cutaneous T-cell lymphoma cell lines mediated by 5-aminolevulinic acid and derivatives

Vallecorsa, Pablo DanielIcon ; Di Venosa, Gabriela MarianaIcon ; Gola, Gabriel; Saenz, Daniel AlbertoIcon ; Mamone, Leandro ArielIcon ; MacRobert, Alexander J.; Ramírez, Javier; Casas, Adriana GabrielaIcon
Fecha de publicación: 08/2021
Editorial: Elsevier Science SA
Revista: Journal of Photochemistry and Photobiology B: Biology
ISSN: 1011-1344
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Medicina Básica

Resumen

The delta-amino acid 5-aminolevulinic acid (ALA), is the precursor of the endogenous photosensitiser Protoporphyrin IX (PpIX), and is currently approved for Photodynamic Therapy (PDT) of certain superficial cancers. However, ALA-PDT is not very effective in diseases in which T-cells play a significant role. Cutaneous T-cell lymphomas (CTCL) is a group of non-Hodgkin malignant diseases, which includes mycosis fungoides (MF) and S´ezary syndrome (SS). In previous work, we have designed new ALA esters synthesised by three-component Passerini reactions, and some of them showed higher performance as compared to ALA. This work aimed to determine the efficacy as pro-photosensitisers of five new ALA esters of 2-hydroxy-N-arylacetamides (1f, 1 g, 1 h, 1i and 1 k) of higher lipophilicity than ALA in Myla cells of MF and HuT-78 cells of SS. We have also tested its effectiveness against ALA and the already marketed ALA methyl ester (Me-ALA) and ALA hexyl ester (He-ALA). Both cell Myla and SS cells were effectively and equally photoinactivated by ALA-PDT. Besides, the concentration of ALA required to induce half the maximal porphyrin synthesis was 209 μM for Myla and 169 μM for HuT-78 cells. As a criterion of efficacy, we calculated the concentration of the ALA derivatives necessary to induce half the plateau porphyrin values obtained from ALA. These values were achieved at concentrations 4 and 12 times lower compared to ALA, according to the derivative used. For He-ALA, concentrations were 24 to 25 times lower than required for ALA for inducing comparable porphyrin synthesis in both CTCL cells. The light doses for inducing 50% of cell death (LD50) for He-ALA, 1f, 1 g, 1 h and 1i were around 18 and 25 J/ cm2 for Myla and HuT-78 cells respectively, after exposure to 0.05 mM concentrations of the compounds. On the other hand, the LD50s for the compound 1 k were 40 and 57 J/cm2 for Myla and HuT-78, respectively. In contrast, 0.05 mM of ALA and Me-ALA did not provoke photokilling since the concentration employed was far below the porphyrin saturation point for these compounds. Our results suggest the potential use of ALA derivatives for topical application in PDT treatment of MF and extracorporeal PDT for the depletion of activated T-cells in SS.
Palabras clave: CANCER , CUTANEOUS T-CELL LYMPHOMA , MYCOSIS FUNGOIDES , PHOTODYNAMIC THERAPY , PORPHYRINS , SÉZARY SYNDROME
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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/168194
DOI: http://dx.doi.org/10.1016/j.jphotobiol.2021.112244
URL: https://www.sciencedirect.com/science/article/abs/pii/S1011134421001238
Colecciones
Articulos(CIPYP)
Articulos de CENTRO DE INVEST. SOBRE PORFIRINAS Y PORFIRIAS
Citación
Vallecorsa, Pablo Daniel; Di Venosa, Gabriela Mariana; Gola, Gabriel; Saenz, Daniel Alberto; Mamone, Leandro Ariel; et al.; Photodynamic therapy of cutaneous T-cell lymphoma cell lines mediated by 5-aminolevulinic acid and derivatives; Elsevier Science SA; Journal of Photochemistry and Photobiology B: Biology; 221; 112244; 8-2021; 1-7
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