Radiolysis, Photolysis & Sonolysis--Cells & Constituents

辐射分解、光解

• 批准号: 6558329
• 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/6558329
• 关键词: amidines; azo compounds; chemical models; combination cancer therapy; cyanides; cytolysis; drug interactions; electron spin resonance spectroscopy; free radical oxygen; free radical scavengers; molecular weight; neoplasm /cancer photoradiation therapy; nonvisual photosensitivity; photolysis; photosensitizing agents; physical chemical interaction; porphyrins; radiosensitizer; solute; surfactant; temperature; tissue /cell culture; ultrasound biological effect; ultrasound therapy; water solution

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 . The surfactant properties of solutes play an important role in the sonochemistry of aqueous solutions. Recently, it has been shown, for relatively low molecular weight surfactants, that these effects can be correlated with the Gibbs surface excess of the solute. We investigated whether this correlation is valid for relatively high molecular weight surfactants, such as sonosensitzers, by considering the Gibbs surface excess and the possible role of the dynamic surface tension using model surfactant molecules, with well characterized surfactant properties. The results show that the Gibbs surface excess of high molecular weight surfactants does not correlate with the extent of decomposition following sonolysis in aqueous solutions. Instead, the decomposition of surfactants depends on their chemical structure and their ability to equilibrate between the bulk solution and the gas/solution interface of cavitation bubbles.

工作概述：声动力疗法是一种很有前景的新型癌症治疗方式，它基于声敏器和超声联合杀伤细胞的协同作用。超声波可以深入组织，并可以聚焦在肿瘤的一个小区域，以激活无毒分子（如卟啉），从而最大限度地减少不良的副作用。实验证据表明，声敏化是由于在热坍缩空化泡内部或附近的声敏化剂被化学激活，通过在水气界面直接热解敏化剂或通过水的热解形成氢原子和羟基自由基的反应而形成敏化剂衍生自由基。来自声敏剂的自由基（主要以碳为中心）与氧反应形成过氧基和烷氧基自由基。与在空化泡内通过热解形成的OH自由基和H原子不同，烷氧基和过氧基自由基在生物介质中与有机化合物的反应活性要低得多，因此它们到达细胞关键部位的可能性更高。最近，我们成功地捕获了各种卟啉水溶液在声波分解过程中形成的碳自由基。