TUMOR PHOTOTHERAPY--NEW PHOTODYNAMIC SENSITIZERS

肿瘤光疗--新型光动力增敏剂

• 批准号: 2092101
• 负责人: MICHAEL A RODGERS
• 金额: $ 13.89万
• 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/2092101
• 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.

这是一个延续申请，涉及发展和 新一代四氮杂卟啉大环化合物的结构表征 其与肿瘤的光动力疗法（PDT）相关。 的 萘酞菁（Nc）和酞菁（Pc）家族被选择用于 这项研究是因为它们强烈的深红色光学反射， 有前途的物理性能，以及它们的稳定性和相容性 具有脂质体和微乳液递送系统。 我们最近的研究 已经确凿地证明，这些家庭的代表是 优良的肿瘤定位剂和促进深红光诱导的肿瘤 低水平坏死。 这些研究将在不同的 程度.一个组件，由M博士指导。E.肯尼，将重点放在 分子合成和表征的新的和发达国家的成员 那些家庭 关于分子光生物学的第二部分将 在鲍灵绿色的私家侦探实验室被跟踪 这将包括 各种地球物理评价均质和 微异质介质，以评估光动力学的有效性。 激光闪光灯和c.w.将采用辐照方法。 第三 由G博士指导。Jori将专注于动物水平的研究， 敏化剂结构和载体对 组织间的药代动力学分布，以及光治疗 选择光敏剂的有效性。 有趣的新问题 需要解决的问题是，深红色吸收化合物是否会 对小鼠色素性黑色素瘤有效。 三个实验室 进行这些研究的地方都有很好的设备 有必要的设施。 这个项目的成果将是一系列新的分子， 关于其PDT有效性的大量定量证据 将被积累。 在另一个层面上，这些信息将是高度 与更深入地理解光动力学机制有关 行动上