TUMOR PHOTOTHERAPY - NEW PHOTODYNAMIC SENSITIZERS

肿瘤光疗——新型光动力敏化剂

• 批准号: 3189514
• 负责人: MICHAEL A RODGERS
• 金额: $ 13.56万
• 依托单位: BOWLING GREEN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3189514
• 关键词: analog; cellular oncology; chemical synthesis; disease /disorder model; evaluation /testing; fluorescence spectrometry; gel filtration chromatography; high performance liquid chromatography; indoles; laboratory mouse; laser spectrometry; liposomes; melanoma; naphthalenes; necrosis; neoplasm /cancer photoradiation therapy; photobiology; photosensitizing agents; phthalocyanin; porphyrins; radiation dosage; singlet oxygen

This is a continuation application that concerns the development and characterization of a new generation of tetraazaporphyrin macrocycles that has relevance to photodynamic therapy (PDT) of tumors. The naphthalocyanine (Nc) and phthalocyanine (Pc) families are selected for this study because of their intense deep-red optical absorptions, their promising photophysical properties, and their stability and compatibility with liposome and microemulsion delivery systems. Our recent studies have demonstrated conclusively that representatives of these families are excellent tumor localizers and promote deep-red-light-induced tumor necrosis at low levels. The studies are to be conducted at a variety of levels. One component, directed by Dr. M. E. Kenney, will focus on molecular synthesis and characterization of new and developed members of the families. A second component concerning molecular photobiology will be followed at the PI's laboratory in Bowling Green. This will include a variety of photophysical evaluations in homogeneous and in microheterogeneous media in order to assess photodynamic effectiveness. Laser flash and c.w. irradiation methods will be employed. The third component, directed by Dr. G. Jori, will focus on animal-level studies on the effects of sensitizer structure and carrier vehicle on the pharmacokinetic distribution among tissues, and on the phototherapeutic effectiveness of selected photosensitizers. An interesting new question to be addressed is whether the deep-red-absorbing compounds will be effective against pigmented melanomas in mice. The three laboratories where these studies are to be carried out are all excellently equipped with the requisite facilities. The outcome of this program will be a series of new molecules about which an abundance of quantitative evidence concerning their PDT effectiveness will be accumulated. At another level this information will be highly relevant to a deeper understanding of the mechanism of photodynamic action.

这是一个继续应用程序，涉及到开发和 新一代四氮杂大环化合物的表征 这与肿瘤的光动力疗法(PDT)有关。这个 选择了萘菁(Nc)和酞菁(Pc)家族用于 这项研究由于它们强烈的深红光吸收，它们的 前景看好的光物理性质及其稳定性和兼容性 使用脂质体和微乳给药系统。我们最近的研究 已经确凿地证明了这些家庭的代表 优秀的肿瘤定位剂和促进深红光诱导的肿瘤 低水平坏死。这些研究将在各种不同的 级别。其中一个组件，由M.E.Kenney博士指导，将专注于 新成员和新成员的分子合成与表征 这些家庭。关于分子光生物学的第二个组成部分将 在保龄格林的私人侦探实验室被跟踪。这将包括一个 均匀和非均匀光物理评估的多样性 微非均相介质，以评估光动力学效果。 激光闪光灯和C.W.将采用辐射方法。第三 组件，由G.Jori博士指导，将专注于动物水平的研究 增感剂结构和载体对感光性能的影响 组织间药代动力学分布及对光疗的影响 精选光敏剂的有效性。一个有趣的新问题 需要解决的问题是，这些深红色吸收化合物是否会 对小鼠的色素黑色素瘤有效。三个实验室 这些研究将在哪里进行，都装备精良 拥有必要的设施。 这一计划的结果将是一系列关于 关于它们的光动力疗法有效性的大量定量证据 将会累积起来。在另一个层面上，这一信息将高度 与更深入地理解光动力学的机理有关 行动。