Mechanism of porphyrin-induced sonodynamic effect: Possible role of hyperthermia
Mechanism of porphyrin-induced sonodynamic effect: Possible role of hyperthermia
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DOI：
10.1667/rr3510.1
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发表时间：
2006-03-01
影响因子：
3.4
通讯作者：
Hynynen, K
中科院分区：
文献类型：
--
作者：
Kinoshita, M;Hynynen, K
超声的生物学效应已被广泛研究，包括组织的热凝固、紧密连接的打开、局部基因或药物的引入。超声波和卟啉衍生物的协同细胞杀伤效应，即所谓的声动力效应，为癌症治疗带来了希望。虽然已经提出了几种解释声动力效应的模型，但其确切机制，特别是在体内的机制仍然未知。我们检测了卟啉衍生物原卟啉IX对超声诱导的HeLa细胞杀伤的影响。在一些实验中，细胞内原卟啉IX浓度通过5-氨基乙酰丙酸处理而增加。虽然细胞外原卟啉IX在微泡增强超声下表现出增强的细胞杀伤作用，但细胞内原卟啉IX则没有。另一方面，细胞内原卟啉IX增强了在中等酸性环境（pH 6.6）下超声暴露可产生的热疗的细胞杀伤作用。由于卟啉衍生物在体内通常会进入细胞内组分，因此我们的研究结果表明，超声引起的热疗可能在卟啉衍生物引起的声动力效应中起重要作用。(C) 2006年由辐射研究学会主办。
The biological effects of ultrasound have been investigated vigorously for various applications including the thermal coagulation of tissues, the opening of tight junctions, and localized gene or drug introduction. The synergistic cell killing effect of ultrasound and porphyrin derivatives, the so-called sonodynamic effect, holds promise for cancer treatment. Although several models to explain the sonodynamic effect have been proposed, its exact mechanism, especially in vivo, remains unknown. We examined the effect of a porphyrin derivative, protoporphyrin IX, on ultrasound-induced killing of HeLa cells. In some experiments, the intracellular protoporphyrin IX concentration was increased by 5-aminolevulinic acid treatment of the cells. Although extracellular protoporphyrin IX showed an enhanced cell killing effect by microbubble-enhanced ultrasound, intracellular protoporphyrin IX did not. On the other hand, intracellular protoporphyrin IX enhanced the cell killing effect of hyperthermia, which can be produced by ultrasound exposure, in a moderately acidic environment (pH 6.6). Because porphyrin derivatives are generally imported into the intracellular component in vivo, our results suggest that hyperthermia caused by ultrasound may play an important role in the sonodynamic effect induced by porphyrin derivatives. (C) 2006 by Radiation Research Society.