5-Aminolevulinic acid-induced oxidative stress on cells by gold nanoparticles.

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5-Aminolevulinic acid (5-ALA) and its methyl ester (5-ALA-Me) at mM concentration levels induce oxidative stress via the production of reactive oxygen species (ROS). Human cancer cell lines (MCF-7 and HepG2) incubated in the dark in the simultaneous presence of 5.0 mM or more of 5-ALA or 5-ALA-Me(for MCF-7) and 7 microg/ml of 15nm citrate capped gold nanoparticles (AuNPs) were damaged more seriously compared to those in the presence of levulinic acid alone. Damage is visible in electron micrographs which reveal similar morphology both in the presence and absence of AuNP's. Cytotoxicity was observed irrespective of the presence or absence of serum and medium. Production of reactive oxygen species ( ROS ) in cell-free samples was monitored by EPR (electron paramagnetic resonance ) as the DMPO-OH spin adduct (DMPO is 5,5-dimethyl-1-pyrroline N-oxide) and also showed a catalytic effect of gold nanoparticles. Both superoxide dismutase and catalase inhibited the production of ROS and also reduced cytotoxicity in the cell samples. These observations can be explained by the initial attack on the cell membrane by ROS produced in the medium outside the cell and provide insight into possible uses of 5-ALA in cancer chemotherapy.