Transport of ALA esters in mammalian cells

CASAS A, RODRÍGUEZ L, DI VENOSA G, BATTAH S, MACROBERT A, BATLLE A.

Hull, Inglaterra

Workshop; Tetrapyrrole Discussion Group; 2005

Tetrapyrrole Discussion Group

The precursor of porphyrins 5-aminolevulinic acid (ALA) is being widely used in Photodynamic Therapy. In addition, esterification of ALA with some aliphatic alcohols leads to improved penetration and selectivity. ALA uptake systems appear to be distinctive for each cell type. In this work we studied ALA derivative transport systems through competence with radiolabelled ALA in the LM3 mammary adenocarcinoma line, which incorporate ALA by BETA transporters. The more lipophilic ALA derivatives Hexyl-ALA and Undecanoyl-ALA compete for ALA uptake, whereas Methyl-ALA, R, S-ALA-2-(hydroximethyl)tetrahydropyranyl ester and the dendron aminomethane tris methyl 5-ALA do not block ALA uptake. However, Hexyl-ALA and Undecanoyl-ALA are not incorporated by BETA transportation, but by passive diffusion although they do block ALA uptake by binding to the cell membrane. These results show that different modifications to the ALA molecule lead to different uptake mechanisms. Whereas ALA is taken up by BETA transportation, none of the ALA derivatives share the same mechanism. The knowledge of the mechanisms of ALA derivatives entrance into the cells is essential to understand and improve ALA-mediated PDT and to design new ALA derivatives that may be incorporated at a higher rate than ALA.