Miyoshi N, Misík V, Fukuda M, Riesz P
Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Radiat Res. 1995 Aug;143(2):194-202.
Sonodynamic therapy is a promising new modality for cancer treatment based on the synergistic effect on tumor cell killing by combination of a drug (typically a photosensitizer) and ultrasound. The mechanism of sonodynamic action was suggested to involve photoexcitation of the sensitizer by sonoluminescent light, with subsequent formation of singlet oxygen. In this work we studied the aqueous sonochemical reactions of the gallium-porphyrin derivative ATX-70, one of the most active sonodynamic agents found, using 50 kHz ultrasound. The experiments were carried out in the presence of 2,2,6,6-tetramethyl-4-piperidone hydrochloride (TMP), which reacts with singlet oxygen or .OH radicals to give the EPR-detectable nitroxide 2,2,6,6-tetramethyl-4-piperidone-N-oxyl (TMP-NO). Recently it has been suggested that the enhancement of TMP-NO yields in the presence of aqueous solutions of ATX-70 exposed to ultrasound was evidence for the formation of singlet oxygen in the system. Our results show that the surfactant cetyltrimethylammonium bromide (CTAB) can mimic the ATX-70-induced increase in the TMP-NO signal, but it fails to reproduce the behavior of ATX-70 in D2O: while the yields of TMP-NO in the presence of ATX-70 increase in D2O, the opposite effect was found with the surfactant CTAB. However, our data show that the increased TMP-NO yields in D2O are paralleled by an increased concentration of ATX-70 dimer, a form that is inactive in the photochemical generation of singlet oxygen. Our finding that the ATX-70-dependent enhancement of the TMP-NO signal was highest at approximately 20% O2, in both N2/O2 and argon/O2 mixtures, and decreased with increasing oxygen concentration is not compatible with the singlet oxygen mechanism. Finally, our results on the temperature dependence of the ATX-70-induced formation of TMP-NO are not consistent with the photochemical excitation of ATX-70 by sonoluminescent light: the ATX-70-dependent enhancement of TMP-NO signal increased with temperature in the range 10-25 degrees C, while the intensity of sonoluminescence of aqueous solutions both in multiple-bubble fields and in single-bubble experiments is known to decrease with increasing temperature.
声动力疗法是一种基于药物（通常是光敏剂）与超声联合对肿瘤细胞杀伤的协同效应的、有前景的癌症治疗新方法。声动力作用机制被认为涉及敏化剂被声致发光光激发，随后形成单线态氧。在这项工作中，我们使用50kHz超声研究了镓卟啉衍生物ATX - 70的水相声化学反应，ATX - 70是已发现的最具活性的声动力剂之一。实验在2,2,6,6 - 四甲基 - 4 - 哌啶酮盐酸盐（TMP）存在下进行，TMP与单线态氧或·OH自由基反应生成可通过电子顺磁共振检测的氮氧化物2,2,6,6 - 四甲基 - 4 - 哌啶酮 - N - 氧基（TMP - NO）。最近有人提出，在暴露于超声的ATX - 70水溶液存在下TMP - NO产率的提高是系统中形成单线态氧的证据。我们的结果表明，表面活性剂十六烷基三甲基溴化铵（CTAB）可以模拟ATX - 70诱导的TMP - NO信号增加，但它无法重现ATX - 70在重水中的行为：虽然在重水中存在ATX - 70时TMP - NO的产率增加，但表面活性剂CTAB的情况则相反。然而，我们的数据表明，重水中TMP - NO产率的增加与ATX - 70二聚体浓度的增加平行，ATX - 70二聚体在单线态氧的光化学产生中是无活性的形式。我们发现在N₂/O₂和氩气/O₂混合物中，ATX - 70依赖的TMP - NO信号增强在约20% O₂时最高，并随氧浓度增加而降低，这与单线态氧机制不相符。最后，我们关于ATX - 70诱导形成TMP - NO的温度依赖性的结果与声致发光光对ATX - 70的光化学激发不一致：在10 - 25℃范围内，ATX - 70依赖的TMP - NO信号增强随温度升高而增加，而在多泡场和单泡实验中，水溶液的声致发光强度已知会随温度升高而降低。
