Retinoblastoma is the most common malignant intraocular
tumor in children. The current treatment gives a good vital prognostic but there are several drawbacks to the arsenal of "classical antitumoral"
therapies.
Photodynamic therapy (
PDT) could be an exciting non-toxic and non-mutagenic alternative protocol.
METHOD: In this paper, we report about the screening of the in vitro photocytotoxicity of hydrophenylporphyrins and chlorins and their glycoconjugated derivatives in a human
retinoblastoma cell line (Y79) and for comparison in a colorectal
adenocarcinoma cell line (HT29).
RESULTS: Despite lower photodynamic activity than that observed for hydroxylated
photosensitizers, in particular
Foscan(®) glycoconjugated derivatives display
phototoxicity (IC50 2.4-0.05μM ±10%) against Y79 cells with examples of significant intrinsic cytotoxicity. Amongst them the triglucosyl
porphyrin 10 is highly photocytotoxic (IC50 0.9μM ±10%) but is fully devoid of cytotoxicity (IC50>15μM). The photoactivity is highly modulated by the presence of a diethyleneglycol spacer between the chromophore and the
glycoside (compounds 14-17, IC50 0.5, 0.6, 0.05 and 0.35μM ±10%) and by the anomeric configuration of the
sugar (compound 15 and 17, IC50 0.6 and 0.05μM ±10% respectively). One of the main problems for the use of
Foscan(®) is its poor solubility which might be improved by glycoconjugation. Moreover
Foscan has been shown to induce
necrosis after
PDT leading to a possible ulceration of surrounding tissues unsuitable for a
conservative treatment. A preferential mitochondrial subcellular localization which has been previously reported for some glycoconjugated
photosensitizers could enhance the contribution of apoptosis process.
CONCLUSION: