Introduction
Photodynamic
therapy (PDT) is a promising new methodology for the treatment of cancer.
PDT has mostly involved the intravenous administration of photosensitizing
agents (porphyrins and structurally related compounds) which tend to be
preferentially accumulated by malignant tissues [1].
A novel approach to PDT involves endogenous photosensitization by administration
of 5-aminolevulinic acid (ALA) which is converted by the heme biosynthesis
pathway to protoporphyrin IX, an efficient photosensitizer [2].
Although ALA-PDT has proved very successful clinically for certain applications
[3],
problems have arisen in treating deeper tumors where ALA applied topically
may not penetrate sufficiently deeply. Attempts to solve this problem are
currently being made by the use of alkylesters of ALA rather than ALA itself
[4]. The use of these esters is however
limited by their toxicity at the high concentrations that must be injected
to compensate for the lack of selectivity. In this poster, we wish to report
the synthesis and use of new ALA derivatives which are able to release
free ALA more selectively. ALA-PEG-esters (PEG = polyethylenglycol) appeared
to be potentially less toxic ALA-esters leading to the production of PpIX
in cells. Moreover, a promising use of ALA-ester-peptide derivatives is
described .
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