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 (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: Tri-α-O-galactosyl porphyrin 16 is a better candidate than Foscan^® for a clinical application of PDT for a conservative therapy of retinoblastoma. [Copyright &y& Elsevier]