The depth of porphyrin in a membrane and the membrane's physical properties affect the photosensitizing efficiency
The depth of porphyrin in a membrane and the membrane's physical properties affect the photosensitizing efficiency
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DOI：
10.1016/s0006-3495(02)75557-4
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发表时间：
2002-04-01
影响因子：
3.4
通讯作者：
Ehrenberg, B
中科院分区：
文献类型：
--
作者：
Lavi, A;Weitman, H;Ehrenberg, B
应用于光动力学治疗的光敏化生物过程是基于驻留在膜上的敏化剂光触发产生分子单线态氧的。目前使用的增敏剂大多是疏水性或两亲性的卟啉及其类似物。短暂的单线态氧的可能活性仅限于它在膜中扩散的时间，然后才出现在水环境中。在这篇文章中，我们展示了新合成的原卟啉衍生物对光敏化过程的增强作用，这些原卟啉衍生物将它们的四吡咯发色团更深地插入脂质体的脂双层。单线态氧的荧光化学靶标9，10-二甲基菲测定其光敏化效率。当双层膜发生熔融相变或被苯甲醇流态化时，由于单线态氧的扩散增强，敏化效率降低。在双层中加入胆固醇或二肉豆蔻基磷脂酰胆碱使卟啉更深入双层；然而，在这两种情况下，随后对敏化效率的影响是不同的。这些结果可能为选择和设计疏水性的膜结合型光敏剂定义一个额外的标准。
Photosensitized biological processes, as applied in photodynamic therapy, are based on light-triggered generation of molecular singlet oxygen by a membrane-residing sensitizer. Most of the sensitizers currently used are hydrophobic or amphiphilic porphyrins and their analogs. The possible activity of the short-lived singlet oxygen is limited to the time it is diffusing in the membrane, before it emerges into the aqueous environment. In this paper we demonstrate the enhancement of the photo sensitization process that is obtained by newly synthesized protoporphyrin derivatives, which insert their tetrapyrrole chromophore deeper into the lipid bilayer of liposomes. The insertion was measured by fluorescence quenching by iodide and the photosensitization efficiency was measured with 9,10-dimethylanthracene, a fluorescent chemical target for singlet oxygen. We also show that when the bilayer undergoes a melting phase transition, or when it is fluidized by benzyl alcohol, the sensitization efficiency decreases because of the enhanced diffusion of singlet oxygen. The addition of cholesterol or of dimyristoyl phosphatydilcholine to the bilayer moves the porphyrin deeper into the bilayer; however, the ensuing effect on the sensitization efficiency is different in these two cases. These results could possibly define an additional criterion for the choice and design of hydrophobic, membrane-bound photosensitizers.