Photodynamic Therapy employing 5-aminolevulinic
acid (ALA) as a precursor of the
photosensitizer Protoporphyrin IX has become a promising approach to treat superficial
cancers. However, the hydrophilic nature of the ALA molecule somewhat limits the penetration through the skin as well as all cell membranes. Different attempts are currently under investigation to enhance ALA penetration, such as the development of new synthetic and more lipophilic molecules derived from ALA and the incorporation of ALA into lipophilic vehicles such as
liposomes. Among the new synthesized molecules, we can find ALA
esters, ALA aminoacid derivatives and ALA
dendrimers. In general, there is consensus that the promising results obtained in vitro with ALA
esters cannot be reproduced in vivo. However, ALA methyl
ester (1) has been widely used for treatment of skin
malignancies and
ALA hexyl ester (15) proved to be more powerful than ALA in bladder imaging. ALA aminoacid derivatives have been designed to use specific cellular
aminopeptidases to targeting
tumors, and it was shown that they can be metabolized to ALA with some specificity.