Radiolysis, Photolysis, Sonolysis and Sonoprotection of

辐射分解、光解、声波分解和声波防护

• 批准号: 7292010
• 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/7292010
• 关键词: Radiolysis; Photolysis; Sonolysis; Sonoprotection

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.The mechanism(s) responsible for sudden cytolysis observed when cells are exposed to ultrasound could be mechanical and/or free radical in nature. Free radical reactions are initiated in the core and in the interfacial regions of collapsing acoustic cavitation bubbles. Since cyclic sugars are known to inhibit free radical chain reactions, we investigated the effect of n-alkyl a-D glucopyranosides of varying hydrophobicity on ultrasound (1.057 MHz) induced cytolysis of HL-60 cells in vitro. n-alkyl glucopyranosides with hexyl- (HGP, 5 mM), heptyl- (3 mM) or octyl- (2 mM) n-alkyl chains protected 100% of the cell population from ultrasound induced cytolysis under conditions where 35% to 100% cytolysis occurred in the absence of glucopyranosides. The protected cell populations also possessed long-term reproductive viability. However, the hydrophilic methyl-a-D glucopyranoside could not protect cells, even up to a concentration of 30 mM. Furthermore, none of the glucopyranosides could prevent cytolysis of cells from a mechanically induced shear stress. Spin trapping and electron spin resonance experiments confirmed the presence of inertial cavitation in cell suspensions both in the presence and absence of the surfactants. It is concluded that surface active glucopyranosides efficiently quench cytotoxic radicals at the gas/solution interface of collapsing 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。当细胞暴露于超声波时，观察到的细胞突然溶解的机制可能是机械的和/或自由基的性质。自由基反应发生在声空化气泡的核心和界面区域。由于已知环糖具有抑制自由基链反应的作用，我们研究了不同疏水性的n-烷基a-D葡萄糖吡喃苷对体外超声（1.057 MHz）诱导HL-60细胞溶解的影响。含有己基- （HGP， 5毫米）、庚基-（3毫米）或辛基-（2毫米）正烷基链的正烷基葡萄糖苷，在不含葡萄糖苷的情况下，35%至100%的细胞溶解发生在超声诱导下，可保护100%的细胞群免受细胞溶解。受保护的细胞群也具有长期的生殖能力。然而，亲水性甲基-a- d葡萄糖苷不能保护细胞，即使达到30 mM的浓度。此外，没有一种葡萄糖苷可以阻止细胞在机械诱导的剪切应力下的细胞溶解。自旋俘获和电子自旋共振实验证实了在表面活性剂存在和不存在的情况下，细胞悬浮液中存在惯性空化现象。结果表明，表面活性葡萄糖苷能有效地抑制空化气泡崩塌时的气/液界面上的细胞毒性自由基。