Radiolysis, Photolysis, Sonolysis and Sonoprotection of

辐射分解、光解、声波分解和声波防护

• 批准号: 7331386
• 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/7331386
• 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.1. Feril, L.B., Tsuda, Y., Kondo, T., Zhao, Q.L., Ogawa, R., Cui, Z.G., Tsukada, K. & Riesz P., Ultrasound-induced killing of monocytic U937 cells enhanced by 2,2'-azobis(2-amidinopropane) dihydrochloride. Cancer Science 95, 181-185 (2004).2. Feril, L., Kondo, T., Takaya, K. & Riesz, P., Enhanced ultrasound-induced apoptosis and cell lysis by a hypotonic medium. International Journal Of Radiation Biology 80, 165-175 (2004).3. Rosenthal, I., Sostaric, J. & Riesz, P., Sonodynamic therapy - a review of the synergistic effects of drugs and ultrasound. Ultrasonics Sonochemistry 11, 349-363 (2004).4. Rosenthal, I., Sostaric, J. & Riesz, P., Enlightened sonochemistry. Research On Chemical Intermediates 30, 685-701 (2004).5. Sostaric, J., Miyoshi, N., Riesz, P., De Graff, W.G., Mitchell, J.B., n-Alkyl glucopyranosides completely inhibit ultrasound induced cytolysis. (Free Radicals Biology and Medicine, In Press, 2005)

工作总结：声动力疗法是一种很有前途的新的癌症治疗方式，其基础是声增敏剂和超声联合作用杀死细胞的协同效应。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。与空化气泡内热解形成的OH自由基和H原子不同，烷氧基和过氧基与生物介质中有机化合物的反应性要低得多，因此它们有更高的概率到达临界细胞位点。当细胞暴露于超声波时观察到的突然细胞溶解的机制可能是机械和/或自由基。自由基反应开始在核心和崩溃的声空化气泡的界面区域。由于已知环状糖抑制自由基链反应，我们研究了不同疏水性的N-烷基α-D吡喃葡萄糖苷对超声（1.057 MHz）诱导的HL-60细胞体外细胞溶解的影响。具有己基-（HGP，5mM）、庚基-（3mM）或辛基-（2mM）正烷基链的正烷基吡喃葡萄糖苷保护100%的细胞群体免受超声诱导的细胞溶解，其中在不存在吡喃葡萄糖苷的情况下发生35%至100%的细胞溶解。受保护的细胞群体也具有长期的繁殖能力。然而，亲水性甲基-α-D吡喃葡萄糖苷不能保护细胞，甚至高达30 mM的浓度。此外，没有一个吡喃葡萄糖苷可以防止细胞从机械诱导的剪切应力的细胞溶解。自旋捕获和电子自旋共振实验证实了在存在和不存在的表面活性剂的细胞悬浮液中的惯性空化的存在。得出的结论是，表面活性的吡喃葡萄糖苷有效地淬灭细胞毒性自由基的气体/溶液界面的崩溃空化气泡。Feril，L.B.，Tsuda，Y.，近藤，T.，Zhao，Q.L.，小川河，崔，Z.G.，冢田湾& Riesz P.，2，2'-偶氮二（2-脒基丙烷）二盐酸盐增强超声对单核细胞U937的杀伤作用Cancer Science 95，181 - 185（2004）。费里尔湖，近藤，T.，Takaya，K. & Riesz，P.，通过低渗介质增强超声诱导的细胞凋亡和细胞溶解。International Journal of Radiation Biology 80，165 - 175（2004）.罗森塔尔岛，Sostaric，J.& Riesz，P.，声动力疗法-药物与超声协同作用的综述。Ultrasonics Sonochemistry 11，349 - 363（2004）.罗森塔尔岛，Sostaric，J.& Riesz，P.，启发声化学。Research On Chemical Intermediates 30，685 - 701（2004）. Sostaric，J.，Miyoshi，N.，Riesz，P.，De Graff，W.G.，Mitchell，J.B.，n-烷基吡喃葡萄糖苷完全抑制超声诱导的细胞溶解。(Free激进分子生物学与医学，出版中，2005年）