Casas A, Di Venosa G, Batlle A, Fukuda H
Centro de Investigaciones sobre Porfirinas y Porfirias, FCEyN, University of Buenos Aires and CONICET, Ciudad Universitaria, Pabellón II, 2do piso, 1428 Buenos Aires, Argentina.
Cell Mol Biol (Noisy-le-grand). 2002 Dec;48(8):931-7.
Benzoporphyrin derivative monoacid ring A (BPD-MA) is a second generation hydrophobic photosensitiser for PDT that has been approved for ocular disease treatment. In the present paper we report the results of in vitro studies on the photosensitising activity of Verteporfin (liposomally formulated BPD-MA) using an adenocarcinoma derived cell line. Our findings show a quick and efficient uptake of Verteporfin by LM3 cells, reaching maxima concentrations after 5 hr exposure to 18 microg Verteporfin/ml. Independently on the concentration, plateau levels are attained 5 hr after exposure to Verteporfin. Exposure of the cells to the photosensitiser appears to be safe in the darkness within a broad range of concentrations. The hydroxyl radical scavenger mannitol afforded the highest protection against PDT, while L-tryptophan, a well known and efficient singlet oxygen quencher was not an effective protector at all, showing scavenging activity only when it was supplemented at concentration as high as 10 mM and when 50% of the cells were affected, showing that in addition to singlet oxygen, which is considered the primary cytotoxic agent in PDT, other interconvertible reactive oxygen specie (ROS), in particular HO are also generated. Verteporfin-PDT also induced morphological features typical of apoptotic cells. Results of the present work show that the LM3 adenocarcinoma cell can be effectively sensitised with Verteporfin-PDT.
苯并卟啉衍生物单酸环A（BPD-MA）是第二代用于光动力疗法（PDT）的疏水性光敏剂，已被批准用于眼部疾病治疗。在本文中，我们报告了使用一种腺癌衍生细胞系对维替泊芬（脂质体配方的BPD-MA）的光敏活性进行体外研究的结果。我们的研究结果表明，LM3细胞能快速有效地摄取维替泊芬，在暴露于18微克维替泊芬/毫升5小时后达到最大浓度。无论浓度如何，暴露于维替泊芬5小时后都会达到平台水平。在很宽的浓度范围内，细胞在黑暗中暴露于光敏剂似乎是安全的。羟基自由基清除剂甘露醇对光动力疗法提供了最高的保护作用，而L-色氨酸，一种众所周知且有效的单线态氧猝灭剂，根本不是有效的保护剂，仅在以高达10毫摩尔的浓度添加且50%的细胞受到影响时才显示出清除活性，这表明除了被认为是光动力疗法中主要细胞毒性剂的单线态氧外，其他可相互转化的活性氧物种（ROS），特别是羟基自由基（HO）也会产生。维替泊芬光动力疗法还诱导了凋亡细胞典型的形态特征。本研究结果表明，LM3腺癌细胞可以被维替泊芬光动力疗法有效致敏。
