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: 6123651
• 负责人: P 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/6123651
• 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

"Sonodynamic therapy is a promising new modality for cancer treatment based on the synergistic effect on cell killing by the combination of a drug (a sonosensitizer; usually a porphyrin) and ultrasound. The effectiveness of sonodynamic therapy has been demonstrated in cell studies and in tumor-bearing animals. The occurrence of acoustic cavitation is a necessary condition for the activation of sonosensitizers. Since the availability of cavitation nuclei in biological systems is very limited we have studied the feasibility of using stabilized microbubbles as potential sources of cavitation nuclei. Stabilized microbubbles are used widely for the enhancement of echo contrast in ultrasound imaging. We have investigated the mechanism of the ultrasound-dependent formation of hydrogen peroxide, hydroxyl radicals and hydrogen atoms ( these species are fingerprints for the occurrence of inertial cavitation in aqueous systems ) in the presence of clinically useful organic echo contrast agents such as Albunex and Levovist at concentrations comparable to those used in ultrasound imaging . In air-saturated solutions, the yields of hydrogen peroxide ( which can be a cell- killing agent above a certain concentration) are enhanced at ultrasound intensities above the cavitation threshold. In addition, the contrast agents themselves undergo combustion reactions in the cavitation bubbles as demonstrated by the formation of methyl radical which were identified by electron paramagnetic resonance methods. Possibly deleterious consequences of the formation of sonochemical intermediates may have to be assessed, particularly because some of the echo contrast agents have been shown to lower the cavitation threshold of diagnostic ultrasound . These results are also relevant with respect to the possible use of such microbubbles in gene therapy, due to the ability of stabilized microbubbles to release their content when exposed to diagnostic ultrasound. Unlike the microspheres formed from organic molecules, inorganic microspheres, Eccospheres, because of their stability and inert nature with respect to participation in free radical processes, appear to be suitable tools for enhancing the yields of aqueous sonochemical reactions."

“声动力疗法是一种很有前途的新方法 用于基于细胞杀伤的协同效应的癌症治疗， 药物（声敏剂;通常是卟啉）的组合 还有超声波声动力疗法的有效性已经被证实， 在细胞研究和荷瘤动物中得到证实。的 声空化的发生是声空化的必要条件。 声敏剂的激活。由于空化的可用性 核在生物系统中是非常有限的，我们已经研究了 使用稳定的微泡作为潜在来源的可行性 空化核稳定的微泡被广泛用于 超声成像中回波对比度的增强。我们有 研究了超声波依赖的形成机制， 过氧化氢、羟基和氢原子（这些 种是惯性空化发生的指纹， 水系统）在存在临床有用的有机回声的情况下 造影剂如Albunex和Levovist， 与超声成像中使用的那些相当。在空气饱和的 溶液，过氧化氢的产率（其可以是细胞- 杀死剂高于一定浓度）的能力增强， 超声强度高于空化阈值。此外，本发明还提供了一种方法， 造影剂本身在造影剂中经历燃烧反应 空化气泡，如通过形成甲基 自由基，通过电子顺磁共振鉴定 方法.形成的可能有害后果 可能必须评估声化学中间体，特别是 因为已经证明某些回波造影剂 降低诊断超声的空化阈值。这些 结果也与可能使用这种方法有关。 微泡在基因治疗中，由于稳定的能力， 微泡在暴露于诊断试剂时释放其内容物 超声.与有机物形成的微球不同 分子，无机微球，Eccospheres，因为它们 在参与自由基方面稳定性和惰性 过程，似乎是提高产量的合适工具， 超声化学反应。"