Hydroxypyridinone and 5‑Aminolaevulinic Acid Conjugates for Photodynamic Therapy

Photodynamic therapy (PDT) is a promising
treatment strategy for
malignant and nonmalignant lesions. 5-Aminolaevulinic acid (ALA) is
used as a precursor of the photosensitizer, protoporphyrin IX (PpIX),
in dermatology and urology. However, the effectiveness of ALA–PDT
is limited by the relatively poor bioavailability of ALA and rapid
conversion of PpIX to haem. The main goal of this study was to prepare
and investigate a library of single conjugates designed to coadminister
the bioactive agents ALA and hydroxypyridinone (HPO) iron chelators.
A significant increase in intracellular PpIX levels was observed in
all cell lines tested when compared to the administration of ALA alone.
The higher PpIX levels observed using the conjugates correlated well
with the observed phototoxicity following exposure of cells to light.
Passive diffusion appears to be the main mechanism for the majority
of ALA–HPOs investigated. This study demonstrates that ALA–HPOs
significantly enhance phototherapeutic metabolite formation and phototoxicity.