Abstract: Phthalocyanines are receiving increasing attention as second-generation sensitizers for photodynamic therapy (PDT). This paper discusses some of the investigations into the mechanism of the phototoxic responses of phthalocyanine-sensitized PDT exploiting the interaction of PDT with other metabolic modulators. Among the agents which interact strongly with PDT is the K$+$PLU$//H$+$PLU$/ ionophore nigericin. Under the conditions studied with chloroaluminum phthalocyanine (AlPcCl), the Na$+$PLU$//H$+$PLU$/ ionophore monensin, the Ca$+$PLU$PLU$/ ionophore A23187, and the lysosomotrophic agent chloroquine, but not the K$+$PLU$/ ionophore valinomycin, also potentiate photodynamic cell killing. None of the latter compounds interact with PDT as strongly as does nigericin. Both nigericin and monensin partially inhibit cellular respiration; however, KCN, which inhibits respiration completely, is less effective in potentiating PDT damage than is nigericin. Nigericin treatment alone does not deplete glutathione; however, the GSH level decreases after treatment of cells with PDT and nigericin. The potentiation of the PDT response is much greater at an extracellular pH (pHe) of 6.70 than at pHe 7.30. When nigericin is present at pHe 6.70, the intracellular pH (pHi) is equilibrated with pHe. None of the other ionophores tested was able to cause the acidification of the intracellular milieu as did nigericin. The evidence to date suggests that the lowering of pHi is an important component of the mechanism by which nigericin potentiates PDT.!
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机译：摘要：酞菁类作为光动力疗法（PDT）的第二代敏化剂受到越来越多的关注。本文探讨了利用PDT与其他代谢调节剂的相互作用研究酞菁敏化PDT的光毒性反应机理的一些研究。与PDT强烈相互作用的试剂中有K $ + $ PLU $ // H $ + $ PLU $ /离子载体尼日尔霉素。在用氯铝酞菁（AlPcCl），Na $ + $ PLU $ // H $ + $ PLU $ /离子载体莫能菌素，Ca $ + PLU $ PLU $ /离子载体A23187和溶菌体营养剂氯喹研究的条件下，但是而不是K $ + $ PLU $ /离子载体缬氨霉素，也可以增强光动力细胞的杀伤力。后一种化合物与PDT的相互作用均不如黑霉素强。黑霉菌素和莫能菌素均能部分抑制细胞呼吸。但是，完全抑制呼吸作用的KCN在增强PDT损伤方面不如黑霉素有效。单独使用尼日利亚霉素治疗不会消耗谷胱甘肽。然而，用PDT和尼日利亚霉素处理细胞后，GSH水平降低。在细胞外pH（pHe）为6.70时，PDT应答的增强作用比在pHe 7.30时增强。当尼古丁在pHe 6.70存在时，细胞内pH（pHi）用pHe平衡。测试的其他离子载体均不能像黑霉素那样引起细胞内环境的酸化。迄今为止的证据表明，pHi的降低是黑素增强PDT的机制的重要组成部分。
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