The use of more lipophilic derivatives of 5-aminolevulinic
acid (ALA) is expected to have better diffusing properties, and after conversion into the parent ALA, to reach a higher
protoporphyrin IX (
PPIX) formation rate, thus improving the efficacy of topical
photodynamic therapy (
PDT). Here we have analysed the behaviour of 3 ALA derivatives (ALA methyl-
ester, hexyl
ester and a 2-sided derivative) regarding
PPIX formation, efficiency in photosensitizing cells and mechanism of cellular death. The maximum amount of
porphyrins synthesized from 0.6 mM ALA was 47 +/- 8 ng/10(5)cells. The same amount was formed by a concentration 60-fold lower of hexyl-ALA and 2-fold higher of methyl-ALA. The 2-sided derivative failed to produce
PPIX accumulation. Applying a 0.6 J cm(-2)light dose, cell viability decreased to 50%. With the 1.5 J cm(-2) light dose, less than 20% of the cells survive, and higher light doses produced nearly total cell killing. Comparing the
PPIX production and the induced
phototoxicity, the more the amount of
porphyrins, the greater the cellular killing, and
PPIX formed from either ALA or ALA-
esters equally sensitize the cells to photoinactivation. ALA-
PDT treated cells exhibited features of apoptosis, independently on the pro-
photosensitizer employed. ALA-
PDT can be improved with the use of ALA derivatives, reducing the amount of ALA necessary to induce efficient
photosensitization.