FAST PHOTOSENSITIZED REACTIONS OF AROMATIC COMPOUNDS

芳香族化合物的快速光敏反应

• 批准号: 3269910
• 负责人: LEONARD I GROSSWEINER
• 金额: $ 10.42万
• 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/3269910
• 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; 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.

光动力疗法治疗肿瘤的分子作用机制 卟啉衍生物(PDT)将使用脂质体和 重新密封红细胞膜(幽灵)。有待研究的增敏剂 与临床PDT密切相关的药物：血卟啉衍生物 (Hpd)，Hpd组分在肿瘤定位和 用聚丙烯酰胺凝胶过滤分离光敏成分 (HPD-A)，以及可能起作用的生物制剂双血卟啉乙醚 (他)。脂质体研究将包括脂质的测量。 这些卟啉及其组分的过氧化和光敏化 对被困住的酶探针造成损坏。将使用激光闪光光解 测量脂质体膜中卟啉形成三重态的方法 以及基于1.27微米发光的单线态氧产生。这个 杂质金属在卟啉光敏化反应中的作用 脂质体的研究将与卟啉的“老化”有关 在稀水介质中导致新的吸收和 荧光条带。关于鬼魂的研究将强调 与脂质有关的活性氧中间体的鉴定 过氧化和蛋白质交联。辐照过程中的即时损坏 并对孵化过程中的延迟损伤进行了描述。结果是 通过结合的卟啉进行光敏化获得的 通过研究产生特定的活性氧剂而得到加强 幽灵外部：单线态氧、超氧化物、羟基自由基 和过氧化氢。在这些调查中推断的机制 应作为评价其光敏化的基础。 蜂窝系统，并指出可能的机制 肿瘤组织中膜的光敏化，其中敏化剂 是HPD及其富集衍生物。