In vitro phototoxicity of glycoconjugated porphyrins and chlorins in colorectal adenocarcinoma (HT29) and retinoblastoma (Y79) cell lines.

Summary Background 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 (IC 50 2.4–0.05 μM ±10%) against Y79 cells with examples of significant intrinsic cytotoxicity. Amongst them the triglucosyl porphyrin 10 is highly photocytotoxic (IC 50 0.9 μM ±10%) but is fully devoid of cytotoxicity (IC 50  > 15 μM). The photoactivity is highly modulated by the presence of a diethyleneglycol spacer between the chromophore and the glycoside (compounds 14 – 17 , IC 50 0.5, 0.6, 0.05 and 0.35 μM ±10%) and by the anomeric configuration of the sugar (compound 15 and 17 , IC 50 0.6 and 0.05 μM ±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 Tri-α- O -galactosyl porphyrin 16 is a better candidate than Foscan ® for a clinical application of PDT for a conservative therapy of retinoblastoma.