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RISS 인기검색어
- 검색키워드
- 저자 : Douillard, Samuel (검색결과 4 건)
- 무료
- 기관 내 무료
- 유료
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In vitro and in vivo evaluation of $Radachlorin^{(R)}$ sensitizer for photodynamic therapy
Douillard, Samuel,Olivier, David,Patrice, Thierry Korean Society of Photoscience 2009 Photochemical & photobiological sciences Vol.8 No.3
This paper reports the evaluation of a new photosensitizer, $Radachlorin^{(R)}$ in comparison with one of its well known components but used solely, Chlorin e6. The photodynamic properties, cell uptake and localisation of the 2 drugs were compared. In vitro studies were conducted on human adenocarcinoma cells (HT-29) and lung carcinoma cell line (A549). Both dyes showed an absorption maximum between 640 and 650 nm, that were enhanced by serum, with a shifted maximum at 661 nm. In vitro, phototoxicities of $Radachlorin^{(R)}$ and Chlorin e6 were nearly identical for HT29 and A549 cells. However, $Radachlorin^{(R)}$ reached its optimal LD50 sooner ($0.59\;{\mu}g\;ml^{-1}$ for 3 h incubation followed by $20\;J\;cm^{-2}$ of 664 nm light ($0.02\;W\;cm^{-2}$)) than Chlorin e6 ($0.60\;{\mu}g\;ml^{-1}$ for 4 h incubation). For in vivo studies, Swiss athymic mice were grafted with human lung carcinoma of the line A549 15 days before intravenous photosensitizer injection. Fluorescence was recorded through an optical fibre spectrofluorimeter using the 666 nm peak for detection. Maximum $Radachlorin^{(R)}$ fluorescence in tumor was observed 2 h after injection ($1412{\pm}31$ AU). Selectivity was expressed by the calculated tumor-to-skin and tumor-to-muscle ratios. Maximum ratios ($1.45{\pm}0.14$ for tumor-to-skin and $1.95{\pm}0.29$ tumor-to-muscle) were observed 7 h after injection with Radachlorin. Maximal Chlorin e6 fluorescence was observed 1 h (shortest time interval measured) after injection in all organs and highest tumor-to-muscle ratio ($2.56{\pm}0.97$) 8 h after injection. Chlorin e6 fluorescence in skin was always at least equivalent to tumor fluorescence. Complete response of grafted tumor was achieved (no recurrence observed during 15 days) after $20\;mg\;kg^{-1}$ IV injection and $200\;J\;cm^{-2}$ irradiation ($0.3\;W\;cm^{-2}$) with both drugs. Optimal delays between injection and light delivery were between 1 and 7 h with $Radachlorin^{(R)}$ and 3 h for Chlorin e6 but severe adverse effects were noted for both drugs when drug?light intervals were shorter than 3 h. This suggests that clinical use would be easier with $Radachlorin^{(R)}$ than Chlorin e6.
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Secondary oxidants in human serum exposed to singlet oxygen: the influence of hemolysis
Olivier, David,Douillard, Samuel,Lhommeau, Isabelle,Bigot, Edith,Patrice, Thierry Korean Society of Photoscience 2009 Photochemical & photobiological sciences Vol.8 No.10
Singlet oxygen ($^1O_2$) is produced by leucocytes during inflammatory reactions, various biochemical reactions and during photoreactions. It deactivates by reacting with a number of targets to produce reactive oxygen species (ROS) and peroxides (that in turn produce ROS). To verify whether serum had the same capability to deactivate secondary oxidants after exposure to $^1O_2$, we provoked a photoreaction using rose bengal added to sera of 53 healthy donors and, after light delivery, reduced 2',7'-dichlorofluorescein (DCFH) was added at the end of irradiation and fluorescence of the oxidized derivative (DCF) was recorded. To avoid optical artifacts, we analyzed the influence of hemolysis. Deactivation capability of secondary oxidants after exposure to $^1O_2$ was stable over a long period of time, slightly different between men and women, but standard biochemistry parameters had little influence. Hemolysis, age and platelet number reduced deactivation of $^1O_2$-induced secondary oxidants. Addition of lysed cancer cells had no influence. Blood sampling in clot act tubes gave a better signal than in heparinized tubes. Red blood cells (RBCs) loaded with antioxidants strongly decreased deactivation of secondary oxidants. Assays are in progress to evaluate the clinical implications of these findings.
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