FAST PHOTOSENSITIZED REACTIONS OF AROMATIC COMPOUNDS

芳香族化合物的快速光敏反应

• 批准号: 3269914
• 负责人: LEONARD I GROSSWEINER
• 金额: $ 11.6万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-05-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3269914
• 关键词: DNA; erythrocyte membrane; flash photolysis; fluorescent dye /probe; free radicals; gel electrophoresis; lasers; light scattering; liposomes; neoplasm /cancer photoradiation therapy; nonvisual photosensitivity; peroxidation; photochemistry; porphyrins; radiation sensitivity; radiosensitizer; singlet oxygen; superoxides; thin layer chromatography; ultraviolet radiation

The molecular action mechanism in photodynamic therapy of tumors with porphyrin derivatives (PDT) will be investigated using liposomes and resealed red blood cell membranes (ghosts). The sensitizers to be studied are closely related to the clinical PDT drugs: hematoporphyrin derivative (HpD), the HpD fraction enriched in the tumor-localizing and photosensitizing constituent separated by polyacrylamide gel filtration (HpD-A), and the putative action biologic agent dihematoporphyrin ether (DHE). The liposome studies will include measurements of lipid peroxidation by these porphyrins and their constituents and photosensitized damage to an entrapped enzyme probe. Laser flash photolysis will be used to measure triplet state formation by the porphyrins in liposome membranes and singlet oxygen generation based on the 1.27 micron luminescence. The role of impurity metals on photosensitization by the porphyrins in liposomes will be investigated in connection with the "aging" of porphyrins porphyrins in dilute aqueous media leading to new absorption and fluorescence bands. The studies with ghosts will emphasize the identification of the active oxygen intermediates responsible for lipid peroxidation and protein cross-linking. Prompt damage during irradation and delayed damage during incubation will be delineated. The results obtained by photosensitization with incorporated porphyrins will be augmented by studies in which specific active oxygen agents are generated externally to the ghosts: singlet oxygen, superoxide, hydroxyl radicals and hydrogen peroxide. The mechanisms deducted in these investigations should serve as a basis for the evaluation of photosensitization of cellular systems and indicate the possible mechanisms for photosensitization of membranes in tumor tissue, in which the sensitizers are HpD and its enriched derivatives.

光动力治疗肿瘤的分子作用机制 卟啉衍生物（PDT）将使用脂质体进行研究， 重新密封的红细胞膜（幽灵）。 待研究的致敏剂 与临床PDT密切相关的药物：血卟啉衍生物 (HpD)，HpD组分富集在肿瘤定位中， 聚丙烯酰胺凝胶过滤分离光敏组分 （HpD-A）和假定作用生物制剂二血卟啉醚 （DHE）。 脂质体研究将包括测量脂质 通过这些卟啉及其组分的过氧化和光敏化 对包埋的酶探针的损害。 将使用激光闪光光解 测量脂质体膜中卟啉形成的三重态 和基于1.27微米发光的单线态氧产生。 的 杂质金属在卟啉光敏化中的作用 脂质体将与卟啉的“老化”联系起来进行研究 卟啉在稀水介质中导致新的吸收， 荧光带 对鬼魂的研究将强调 负责脂质的活性氧中间体的鉴定 过氧化和蛋白质交联。 辐照时的瞬发损伤 以及孵化期间的延迟损伤。 结果 通过与掺入卟啉的光敏化获得， 通过产生特定活性氧剂的研究， 外部的鬼：单线态氧，超氧化物，羟基自由基 和过氧化氢。 在这些调查中推断出的机制 应作为评价光敏性的基础， 细胞系统，并指出可能的机制， 肿瘤组织中的膜的光敏化，其中敏化剂 是血卟啉及其浓缩衍生物。