Photodynamic therapy: Regulation of porphyrin synthesis and hydrolysis from ALA esters

Photodynamic therapy (PDT) is a tool for the treatment of certain cancerous and pre-cancerous conditions. The natural precursor of porphyrins 5-aminolevulinic acid (ALA) has been extensively used as a pro-photosensitiser in PDT. ALA’s poor permeability has been enhanced by chemical esterification wi...

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Bibliographic Details
Published in:Journal of photochemistry and photobiology. B, Biology Biology, 2006-05, Vol.83 (2), p.129-136
Main Authors: Di Venosa, Gabriela, Fukuda, Haydée, Batlle, Alcira, MacRobert, Alexander, Casas, Adriana
Format: Article
Language:English
Subjects:
Adenocarcinoma - drug therapy
Adenocarcinoma - metabolism
ALA
ALA derivative
Aminolevulinic acid
Aminolevulinic Acid - analogs & derivatives
Aminolevulinic Acid - metabolism
Animals
Biological Transport, Active
Cell Line, Tumor
Female
Hydrolysis
Kinetics
Mammary Neoplasms, Experimental - drug therapy
Mammary Neoplasms, Experimental - metabolism
Mice
Models, Biological
PDT
Photochemotherapy
Photodynamic therapy
Porphyrins - biosynthesis
Porphyrins - metabolism
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Summary:Photodynamic therapy (PDT) is a tool for the treatment of certain cancerous and pre-cancerous conditions. The natural precursor of porphyrins 5-aminolevulinic acid (ALA) has been extensively used as a pro-photosensitiser in PDT. ALA’s poor permeability has been enhanced by chemical esterification with aliphatic alcohols. Some of the ALA esters proved to be more efficient than ALA for porphyrin synthesis. In the present work we studied the nature of porphyrin synthesis regulation from the ALA esters Hexyl-ALA (He-ALA) and R, S-ALA-2-(hydroxymethyl)tetrahydropyranyl ester (THP-ALA) in an adenocarcinoma cell line. We found that He-ALA is incorporated into the cells at a higher rate, followed by THP-ALA and ALA, whereas ALA and ALA esters efflux at the same rate mediated by passive diffusion. Although ALA entrance to the cell might be regulatory at low concentrations, ALA derivative uptake is not a limiting factor. At high concentrations, the regulation of ALA conversion into porphyrins is driven by the enzyme porphobilinogenase, whereas ALA esters hydrolysis is regulated by esterases. The key conclusion of this contribution is that the use of ALA esters has to be limited to low concentrations where no regulation on porphyrin synthesis takes place.
ISSN:1011-1344
1873-2682
DOI:10.1016/j.jphotobiol.2006.01.002