Radiolysis, Photolysis and Sonolysis of Cells and their

细胞的辐射分解、光解和声分解及其作用

• 批准号: 6756260
• 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/6756260
• 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. It is known that the ultrasound frequency affects the number of radicals that can be produced during sonolysis and the efficiency of sonodynamic therapy. A major limitation in determining effects of ultrasound frequency in sonochemistry due to cavitation is the absence of a relationship between the energy supplied to the system and the energy converted by the cavitation process into a sonochemical effect. Recently we have found a frequency effect which is independent of the energy supplied to the system. Spin trapping of secondary carbon radicals with 3,5-dibromo-4-nitrosobenzenesulfonic acid and electron paramagnetic resonance have been used to determine the relative ability of 2 non-volatile surfactants [sodium 1-pentanesulfonic acid (SPSo) and sodium dodecyl sulfate (SDS)] to scavenge H atoms and OH radicals at the gas/solution interface of cavitation bubbles at 3 frequencies ( 47, 354 and 1057 kHz ). At specific bulk concentrations the surfactants reach a limiting plateau value in radical scavenging ability. At 354 and 47 kHz the magnitude of this plateau was greater for SPSo than for SDS. However at 1057 kHz no difference in the plateau values was observed.. Thus at the plateau concentrations the relative ability of these n-alkyl chain surfactants to scavenge radicals at the gas/solution interface of cavitation bubbles depends on the ultrasound frequency but is independent of the ultrasound intensity. These observations can be explained in terms the effect of the rate of change of the surface area of "high energy stable cavitation bubbles" at different ultrasound frequencies on the ability of surfactants to accumulate at the gas/solution interface of cavitation bubbles.

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氢原子和羟基的反应而形成敏化剂衍生的自由基 由水热解形成的自由基。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。已知超声频率影响在声解过程中可以产生的自由基的数量和声动力治疗的效率。 确定声化学中由于空化引起的超声频率的影响的主要限制是供应给系统的能量与通过空化过程转换成声化学效应的能量之间不存在关系。最近，我们发现了一种频率效应，它与系统所受的能量无关。用3，5-二溴-4-亚硝基苯磺酸对仲碳自由基的自旋捕获和电子顺磁共振技术测定了2种非挥发性表面活性剂[1-戊磺酸钠（SPSO）和十二烷基硫酸钠（SDS）]在3个频率下对空化气泡气/液界面上OH和H原子的相对捕获能力（47、354和1057 kHz）。在特定的体积浓度下，表面活性剂达到自由基清除能力的极限平台值。在354和47 kHz时，SPSO的该平台的幅度大于SDS。然而，在1057 kHz下，没有观察到平台值的差异。因此，在平台浓度下，这些n-烷基链表面活性剂在空化气泡的气体/溶液界面处抑制自由基的相对能力取决于超声频率，但与超声强度无关。这些观察结果可以用不同超声频率下“高能稳定空化气泡”表面积的变化率对表面活性剂聚集能力的影响来解释 在空化气泡的气体/溶液界面处。