FAST PHOTOSENSITIZED REACTIONS OF AROMATIC COMPOUNDS

芳香族化合物的快速光敏反应

• 批准号: 3269915
• 负责人: LEONARD I GROSSWEINER
• 金额: $ 13.9万
• 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 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3269915
• 关键词: DNA; acetylation; cell membrane; chromophore; erythrocyte membrane; erythrocytes; flash photolysis; fluorescent dye /probe; gel electrophoresis; lasers; light scattering; liposomes; membrane proteins; neoplasm /cancer photoradiation therapy; nonvisual photosensitivity; peroxidation; photochemistry; phototherapy; porphyrins; psoriasis; pyridine; radiation sensitivity; radiosensitizer; sodium; thin layer chromatography; ultraviolet radiation

The objective in a phototherapy procedure is to deliver the light dose to the tissue that accomplishes the desired clinical objective, e.g., in "PUVA" therapy of psoriasis, light therapy of neonatal jaundice, and photodynamic therapy (PDT) of malignant tumors. Tissues are optically turbid media, in which the disposition of radiant energy depends on the light scattering and absorption properties, the dimensions, and interfaces with external media. The utilization of light by chromophores embedded in tissues can be investigated with the experimental and analytical methods of tissue optics. A diffuse optics spectrophotometer utilizing integrating spheres and optical fiber probe methods will be used for the measurements, and the results will be analyzed with the diffusion approximation for radiative transfer. These techniques will be applied to in vitro systems that model the photophysical and photochemical stages of PDT at the molecular level. Tissue phantoms consisting of light scattering liposomes and resealed beef erythrocyte membranes incorporating a hematoporphyrin derivative (HPD) preparation, and selected alternative PDT sensitizers, will be employed to study the effects of wavelengths, sensitizer concentration, and photobleaching on photodynamic efficiency. The HPD preparations to be investigated include the clinical drug Photofrin II, HPD enriched in the active "dihematoporphyrin ether" (DHE) constituent by gel column chromatography, 99% DHE prepared on an a Sephadex LH-20 column (provided by Dr. D. Kessel), and HPD with a high ester content prepared by acetylation with acetic anhydride in pyridine. Lipid peroxidation, cross-linking of ghost proteins, and photoinactivation of exogenous enzyme probes will be employed for damage evaluation. Similar experiments will be done with biological tissues incorporating photosensitizers, including potato slabs and pig skin. The project includes the further development of analytical optical dosimetry models for PDT treatment planning. The models will be tested at the photophysical level with tissue phantoms, and evaluated for applicability be retrospective comparison to on-going PDT trails.

光疗程序的目的是传递光线 达到预期临床目标的组织的剂量， 例如，在牛皮癣的PUVA疗法中，新生儿的光疗法 以及恶性肿瘤的光动力疗法(PDT)。 组织是光学混浊的介质，在其中处置 辐射能量取决于光的散射和吸收。 属性、维度以及与外部介质的接口。 嵌入组织中的发色团对光的利用可以 用实验和分析的方法来研究 组织光学。一种利用漫反射光学技术的分光光度计 将使用积分球和光纤探测法 用于测量，结果将使用 辐射传递的扩散近似。这些技术 将被应用于模拟光物理的体外系统 以及在分子水平上的光化学阶段。组织 由光散射脂质体组成的模体并重新密封 含有血卟啉的牛肉红细胞膜 衍生物(HPD)制剂和选定的替代光动力疗法 感光剂，将被用于研究波长的影响， 感光剂浓度和光漂白对光动力的影响 效率。拟调查的HPD制剂包括 临床药物Photofrin II，Hpd活性丰富 凝胶柱分离“双血卟啉醚”(DHE)组分 层析，99%DHE在Sephadex LH-20上制备 色谱柱(D.Kessel博士提供)和高酯的HPD 通过与乙酸酐在吡啶中进行乙酰化而制备的含量。 脂质过氧化，幽灵蛋白的交联，以及 将使用外源酶探针的光灭活 进行损害评估。类似的实验将在 含有光敏剂的生物组织，包括土豆 薄片和猪皮。该项目包括进一步的开发 用于PDT治疗的分析光学剂量学模型 计划。这些模型将在光物理水平上进行测试 使用组织模体，并评估其适用性 与正在进行的PDT试验的回顾比较。