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3 results on '"Laville I"'

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

Author

Maillard, Ph., Loock, B., Grierson, D.S., Laville, I., Blais, J., Doz, F., Desjardins, L., Carrez, D., Guerquin-Kern, J.-L., and Croisy, A.

Subjects
CELL culture, CULTURES (Biology), CYTOLOGICAL techniques, CELL lines
Abstract

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]

Published
2007
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2. Biodistribution of meta-tetra(hydroxyphenyl)chlorin incorporated into surface-modified nanocapsules in tumor-bearing mice

Author

Bourdon, O., Laville, I., Carrez, D., Croisy, A., Fedel, Ph., Kasselouri, A., Prognon, P., Legrand, P., and Blais, J.

Abstract

meta-Tetra(hydroxyphenyl)chlorin (mTHPC), a second generation photosensitizer used in photodynamic therapy (PDT), was incorporated into long circulating carriers with the aim of improving the tumor selectivity by limiting the reticuloendothelial system (RES) uptake. Biodistribution of mTHPC (0.06 mg kg−1) was studied directly in nude mice bearing HT29 human tumor by optical fiber fluorimetry and tissue drug contents were determined by HPLC after extraction. The drug was incorporated in the oily core of nanocapsules surrounded by poly(D,L lactic acid) (PLA NCs), PLA grafted with polyethylene glycol (PLA-PEG) or PLA coated with poloxamer 188 (polox PLA). Compared to PLA NCs, incorporation of mTHPC in surface-modified nanocapsules resulted in strong modifications of the drug biodistribution and tumoral retention with a three-fold increase of drug level as early as 24 h post-administration. A reduced liver uptake was observed at early times post-administration indicating that surface-modified NCs are effective in limiting the RES uptake and could be potential carriers to enhance the therapeutic ratio of lipophilic photosensitizers. Furthermore, in situ fluorescence measurements and concentration data were found in broad agreement showing that optical fiber fluorimetry is a very sensitive method that can be used to follow the biodistribution of fluorescent drugs in real-time.

Published
2002
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3. Biodistribution of meta-tetra(hydroxyphenyl)chlorin incorporated into surface-modified nanocapsules in tumor-bearing mice

Author

Bourdon, O., Laville, I., Carrez, D., Croisy, A., Fedel, Ph., Kasselouri, A., Prognon, P., Legrand, P., and Blais, J.

Abstract

meta-Tetra(hydroxyphenyl)chlorin (mTHPC), a second generation photosensitizer used in photodynamic therapy (PDT), was incorporated into long circulating carriers with the aim of improving the tumor selectivity by limiting the reticuloendothelial system (RES) uptake. Biodistribution of mTHPC (0.06 mg kg−1) was studied directly in nude mice bearing HT29 human tumor by optical fiber fluorimetry and tissue drug contents were determined by HPLC after extraction. The drug was incorporated in the oily core of nanocapsules surrounded by poly(d,llactic acid) (PLA NCs), PLA grafted with polyethylene glycol (PLA-PEG) or PLA coated with poloxamer 188 (polox PLA). Compared to PLA NCs, incorporation of mTHPC in surface-modified nanocapsules resulted in strong modifications of the drug biodistribution and tumoral retention with a three-fold increase of drug level as early as 24 h post-administration. A reduced liver uptake was observed at early times post-administration indicating that surface-modified NCs are effective in limiting the RES uptake and could be potential carriers to enhance the therapeutic ratio of lipophilic photosensitizers. Furthermore, in situfluorescence measurements and concentration data were found in broad agreement showing that optical fiber fluorimetry is a very sensitive method that can be used to follow the biodistribution of fluorescent drugs in real-time.

Published
2002
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