Brasseur N, Ouellet R, Lewis K, Potter W R, van Lier J E
MRC Group in the Radiation Sciences, Faculty of Medicine, University of Sherbrooke, Québec, Canada.
Photochem Photobiol. 1995 Dec;62(6):1058-65. doi: 10.1111/j.1751-1097.1995.tb02409.x.
The photodynamic therapy (PDT) activity of the bis(dimethylthexylsiloxy)silicon 2,3-naphthalocyanine (SiNc 8) was evaluated against the EMT-6 tumor implanted intradermally in BALB/c mice. The SiNc 8 was formulated in aqueous emulsions based on Cremophor EL or Solutol HS 15. The formulation was shown to affect plasma clearance and overall pharmacokinetics. Compared to Cremophor, Solutol promoted rapid plasma clearance and high liver retention of the dye, combined with a slight increase of dye tumor concentrations. The PDT action spectrum for tumor response of SiNc 8 in Cremophor (190 mW cm-2, 200 J cm-2, 24 h postinjection [p.i.] of 1 mumol kg-1) showed a maximum at 780 nm, which corresponds to the absorption maximum of the monomeric dye as well as the in vivo maximum change in the "diffuse optical density" produced by the dye. The extent of tumor necrosis increased with augmented dye and light doses. Regardless of the formulation, at 1 h p.i. of 0.1 mumol kg-1 SiNc 8, PDT efficiency (190 mW cm-2, 400 J cm-2) was high but accompanied by severe damage to normal tissues, at 24 h p.i. PDT resulted in complete tumor regression in 80% of the animals without adverse effects to adjacent tissues, while at 72 h p.i. PDT induced no tumor response with Cremophor and only a partial response with Solutol. At the latter time point, plasma dye clearance was nearly complete while tumor tissue levels remained high, suggesting that tumor response correlates with plasma rather than tumor dye levels. Skin sensitivity of SKhI mice to solar-simulated radiation was lower with SiNc 8 as compared to Photofrin. Our data suggest the potential of SiNc 8 as a far-red absorbing photosensitizer in clinical PDT.
评估了双（二甲基叔己基硅氧基）硅2,3-萘酞菁（SiNc 8）对BALB/c小鼠皮内植入的EMT-6肿瘤的光动力疗法（PDT）活性。SiNc 8被制成基于聚氧乙烯蓖麻油EL或聚乙二醇单硬脂酸酯HS 15的水包乳剂。该制剂显示会影响血浆清除率和整体药代动力学。与聚氧乙烯蓖麻油相比，聚乙二醇单硬脂酸酯促进了染料的快速血浆清除和肝脏高保留率，同时染料在肿瘤中的浓度略有增加。SiNc 8在聚氧乙烯蓖麻油中（190 mW/cm²，200 J/cm²，注射1 μmol/kg后24小时）对肿瘤反应的PDT作用光谱在780 nm处显示最大值，这对应于单体染料的吸收最大值以及染料产生的“漫射光密度”的体内最大变化。肿瘤坏死程度随染料和光剂量的增加而增加。无论制剂如何，在注射0.1 μmol/kg SiNc 8后1小时，PDT效率（190 mW/cm²，400 J/cm²）很高，但伴有对正常组织的严重损伤，在注射后24小时，PDT使80%的动物肿瘤完全消退，对相邻组织无不良影响，而在注射后72小时，聚氧乙烯蓖麻油组PDT未诱导肿瘤反应，聚乙二醇单硬脂酸酯组仅产生部分反应。在后者时间点，血浆染料清除几乎完成，而肿瘤组织水平仍然很高，这表明肿瘤反应与血浆而非肿瘤染料水平相关。与卟吩姆钠相比，SiNc 8使SKhI小鼠对模拟太阳辐射的皮肤敏感性降低。我们的数据表明SiNc 8作为临床PDT中一种吸收远红光的光敏剂具有潜力。
