Photosensitization of pancreatic tumour cells by delta-aminolaevulinic acid esters

A series of straight chain, branched and cyclo-delta -aminolaevulinic acid (ALA) esters have been synthesized and their photosensitizing properties an alysed using an in vitro system of rat pancreatoma cells. Structurally favo urable ALA esters not only induced the formation of more of the endogenous photosensitizer, protoporphyrin IX (PpIX), but they did so at a faster rate than ALA itself. This action was reflected in a substantial increase in ph otocytotoxicity of some 270 times, using the more potent ALA esters, An imp ortant structural feature was identified in two of the ALA esters which gre atly limited PpIX production, i,e, a branch point located next to the site of ester cleavage. Experiments on the transport of ALA and of ALA esters ac ross the cell membrane showed that ALA, but not ALA esters, gain access to the cell via the di- and tripeptide transporter, PEPT1, Finally, these resu lts show that the esterification of ALA can greatly increase its cellular u ptake, so generating more intracellular PpIX, improved tumour cell photosen sitization and enhanced photocytotoxicity.