Uzdensky A B, Dergacheva O Y, Zhavoronkova A A, Reshetnikov A V, Ponomarev G V
Department of Biophysics, Rostov State University, 194/1, Stachky ave., NIINK, Rostov-on-Don, 344090, Russia.
Life Sci. 2004 Mar 12;74(17):2185-97. doi: 10.1016/j.lfs.2003.09.053.
Chlorin e(6) and its derivatives are promising sensitizers for photodynamic therapy (PDT). In order to compare the photodynamic effects of 8 novel derivatives of chlorin e(6) and to explore some mechanisms of their effects at the cellular level, we studied PDT-induced changes in bioelectric activity of crayfish mechanoreceptor neuron that was used as a sensitive experimental model. Neurons were insensitive to red laser irradiation (632.8 nm; 0.3 W/cm(2)) or to photosensitizers alone, but changed firing rate and died under the photodynamic effect of nanomolar concentrations of sensitizers. The dynamics of neuron responses depended on photosensitizer type and concentration. The dependence of neuron lifetime on photosensitizer concentration allowed comparing efficiencies of different photosensitizers. Radachlorin was the most potent photosensitizer comparable with mTHPC. High photodynamic efficiency of some chlorin e(6) derivatives was related to weak dependence of neuron lifetime on sensitizer concentration, indicating to the initiation of 2-3 secondary processes such as free radical membrane damage by one absorbed photon. Photodynamic efficiency of sensitizers depended on amphiphilicity influencing their intracellular localization.
二氢卟吩e（6）及其衍生物是有前景的光动力疗法（PDT）敏化剂。为了比较8种新型二氢卟吩e（6）衍生物的光动力效应，并在细胞水平探索其作用的一些机制，我们研究了以小龙虾机械感受器神经元作为敏感实验模型的光动力疗法诱导的生物电活动变化。神经元对红色激光照射（632.8nm；0.3W/cm²）或单独的光敏剂不敏感，但在纳摩尔浓度的敏化剂的光动力作用下，放电频率改变并死亡。神经元反应的动力学取决于光敏剂的类型和浓度。神经元寿命对光敏剂浓度的依赖性使得能够比较不同光敏剂的效率。二氢卟吩e6是与间-四羟基苯基氯高铁卟啉相当的最有效的光敏剂。一些二氢卟吩e（6）衍生物的高光动力效率与神经元寿命对敏化剂浓度的弱依赖性有关，这表明一个吸收光子引发了2-3个次级过程，如自由基膜损伤。敏化剂的光动力效率取决于影响其细胞内定位的两亲性。
