Radiolysis, Photolysis and Sonolysis of Cells and their Constituents

细胞及其成分的放射分解、光分解和声分解

• 批准号: 6433346
• 负责人: PETER RIESZ
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6433346
• 关键词: amidines; azo compounds; combination cancer therapy; cyanides; cytolysis; drug interactions; electron spin resonance spectroscopy; free radical oxygen; free radical scavengers; neoplasm /cancer photoradiation therapy; nonvisual photosensitivity; photolysis; photosensitizing agents; porphyrins; radiosensitizer; temperature; tissue /cell culture; ultrasound biological effect; ultrasound therapy

Summary of work: Sonodynamic therapy is a promising new modality for cancer treatment based on the synergistic effects of cell killing by a combination of sonosensitzer and ultrasound. Ultrasound can penetrate deeply into tissue and can be focused in a small region of tumor to activate non-toxic molecules (e.g. porphyrins ) thus minimizing undesirable side effects. The experimental evidence suggests that sonosensitization is due to the chemical activation of sonosensitizers inside or in close vicinity of hot collapsing cavitation bubbles to form sensitizer-derived radicals either by direct pyrolysis of the sensitizer at the water-gas interface or due to the reactions of hydrogen atoms and hydroxyl radicals formed by the pyrolysis of water. The free radicals derived from the sonosensitizer (mostly carbon-centered) react with oxygen to form peroxyl and alkoxyl radicals. Unlike OH radicals and H atoms which are formed by pyrolysis inside cavitation bubbles, the reactivity of alkoxyl and peroxyl radicals with organic compounds in biological media is much lower and hence they have a higher probability of reaching critical cellular sites. Recently we have succeeded in spin-trapping the carbon radicals formed during the sonolysis of aqueous solutions of various porphyrins .Umemura et al have proposed that the sonoluminescent light produced during cavitational collapse of microbubbles is responsible for the photoexcitation of the sensitizer, with subsequent formation of singlet oxygen, a known reactive cytotoxic species. We recently obtained further evidence against the singlet oxygen mechanism of Umemura by studying the sonolysis of aqueous oxygen-saturated solutions of Hematoporphyrin and Rose Bengal in 90% D2O using a sensitive new reagent which reacts specifically with singlet oxygen to produce an EPR detectable signal .Our results were inconsistent with a major role for singlet oxygen formation in the sonolysis of these compounds. The role of the hydrophobicity of sonosensitzers in determining their accumulation at the water - gas interface of ultrasound-induced cavitation bubbles is being studied by considering the Gibbs surface excess and the possible role of the dynamic surface tension using model surfactant molecules.Recent Publications:Misik,V., Miyoshi,N. and Riesz,P. Free Rad Biol Med 26:961-67, 1999.Misik,V. and Riesz,P. in "Sonochemistry and Sonoluminescence"ed.L.A.Crum et al. (eds.) NATO ASI Series,Kluwer Academic Publishers, 225-236, 1999Misik, V. and Riesz, P. Ann. New York Acad. Sci., 899:335-348, 2000.Miyoshi, N., Igarashi, T. and Riesz, P. Ultrasonics-Sonochemistry, 7:121-124, 2000.

工作总结：声动力学疗法是一种基于声敏剂和超声联合杀伤细胞的协同效应的有前途的癌症治疗新模式。超声波可以深入组织，并可以集中在肿瘤的一个小区域，以激活无毒分子（例如卟啉），从而最大限度地减少不良副作用。实验证据表明，声增敏是由于热塌陷空化气泡内部或附近的声增敏剂的化学活化，通过在水-气界面处的敏化剂的直接热解或由于水的热解形成的氢原子和羟基自由基的反应而形成敏化剂衍生的自由基。来自声敏剂的自由基（主要是碳中心的）与氧反应以形成过氧基和烷氧基自由基。与在空化气泡内通过热解形成的OH自由基和H原子不同，烷氧基和过氧基与生物介质中的有机化合物的反应性低得多，因此它们具有更高的到达临界细胞位点的概率。最近，我们已经成功地在自旋捕获过程中形成的碳自由基的各种卟啉的水溶液的sonolysis。Umemura等人提出，声致发光的光产生的微泡空化崩溃的敏化剂的光激发，与随后形成单线态氧，一个已知的反应性细胞毒性物种。最近，我们通过研究血卟啉和玫瑰红在90%D_2O中的氧饱和水溶液的超声分解，获得了反对Umemura的单线态氧机制的进一步证据，我们的结果与单线态氧形成在这些化合物的超声分解中的主要作用不一致。通过考虑吉布斯表面过剩和使用模型表面活性剂分子的动态表面张力的可能作用，正在研究声敏剂的疏水性在确定它们在超声诱导空化气泡的水-气界面处的积累中的作用。Miyoshi，N.和Riesz，P. Free Rad Biol Med 26：961-67，1999.Misik，V.和Riesz，P.在“Sonochemistry and Sonoluminescence“艾德编. L. A. Crum等（编）NATO ASI Series，Kluwer Academic Publishers，225-236，1999 Misik，V. and Riesz，P. Ann.纽约科学院.科学，899：335-348，2000. Miyoshi，N.，伊加拉斯，T.和Riesz，P. Ultrasonics-Sonochemistry，7：121-124，2000。