Porphyrin synthesis from aminolevulinic acid esters in endothelial cells and its role in photodynamic therapy.

RODRIGUEZ L; DE BRUIJN H; DI VENOSA G; MAMONE L; ROBINSON D; JUARRANZ A; BATLLE A; CASAS A

JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY

Elsevier Sequoia

Año: 2009 vol. 96 p. 249 - 254

1011-1344

Photodynamic therapy (PDT) may cause tumour cell destruction by direct toxicity or by inducing microcirculatoryshutdown. Protoporphyrin IX generated from 5-aminolevulinic acid (ALA) has been widelyused as an endogenous photosensitiser in PDT. However, the hydrophilic nature of the ALA molecule limitsits penetration through the stratum corneum of the skin and cell membranes and thus, ALA alkyl-estershave been developed to improve ALA permeation.The aim of this work was to study Protoporphyrin IX synthesis from ALA and its derivatives ALA methylester (Me-ALA) and ALA hexyl ester (He-ALA) in the microvascular endothelial cell line HMEC-1 derivedfrom normal skin, and to evaluate their response to PDT.We found that lower light doses are required to photosensitise HMEC-1 endothelial cells than to photosensitisePAM212 transformed keratinocytes, showing some possible selectivity of ALA-PDT for vascularisationin skin.Employed at concentrations leading to equal Protoporphyrin IX synthesis, ALA, He-ALA and Me-ALApresented the same efficacy of HMEC-1 photosensitisation. However, He-ALA was a promising compoundfor the use in the enhancement of Protoporphyrin IX in HMEC-1 cells employed at low concentrations atboth short and long time exposures whereas Me-ALA should be employed at high concentrations andlonger time periods in order to surpass the Protoporphyrin IX levels obtained with ALA. The advantageof Me-ALA over ALA was based on its lower dark toxicity.This is the first work to report vascular cell photosensitisation employing alkyl-esters of ALA, and wedemonstrated that these derivatives could exert the same effect as ALA and under certain conditionsenhance photosensitisation of vasculature.