TARGETED PHOTODYNAMIC ACTION

定向光动力作用

• 批准号: 3179080
• 负责人: DOUGLAS C NECKERS
• 金额: $ 8.13万
• 依托单位: BOWLING GREEN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3179080
• 关键词: breast neoplasms; chromophore; ligands; monoclonal antibody; neoplasm /cancer photoradiation therapy; nonvisual photosensitivity; respiratory oxygenation

"Photoradiation therapy is therapy requiring the use of a photosensitizer to elicit a therapeutic effect when the sensitizer is activated by photons in the visible region of the spectrum." Its recent use was pioneered by Dougherty who reported that fluorescein derivatives could be activated by 488 nm light to reduce the growth rate of mammary in mice1 and that hematoporphyrin derivative could be activated with red light to cause complete eradication of mammary tumors in mice and rats. Rose bengal is a xanthene dye whose properties have been studied in detail by Neckers. It is a useful sensitizer for singlet oxygen formation in many different solvents and molecular forms, including polymeric ones. Its structure can be modified easily and structural changes cause little change in photochemical or photophysical characteristics. It is a purpose of this proposal to further develop the chemistry of this dye, which like most dyes, is very complicated. We intend to make it the prototypical dye system on which future dye modifications and chemistries for phototherapeutic applications can be based. It is our intention to demonstrate that by proper structural modification this sensitizer can be directed to specific oxidizable substrates to increase the selectivity of oxidation of a specific partner molecule, and use this targeted photosensitizer concept to alter the rate of, and products obtained from, these oxidation processes. We call this the principle of targeted photodynamic action. Rose bengal, 4, will be functionalized to react with enzymes and antibodies and these will be used to attract selectively other molecular entities such as substrates, inhibitors, or antigens. This should attract these latter entities to the site of the sensitizer functionalized enzyme, or antibody, and hence to the source of singlet oxygen. It should enhance the local concentration of the potential singlet oxygen acceptor in the vicinity of the source - the sensitizer. We intend to apply this principle, Targeted Photodynamic Action, in tumor phototherapy. Collaborations are arranged with 1. Dougherty (photodynamic therapy), C. W. Lin (bladder cancer phototherapy), and J. Spikes (xanthene dye incorporation into liposomes), and A. Oseroff (functionalized monoclonal antibodies).

光放射疗法是一种需要使用光敏剂的疗法。 当增敏剂被光子激活时产生治疗效果 在光谱的可见光区。它最近的用法是由 多尔蒂报告说，荧光素衍生品可以通过 488 nm光对小鼠乳腺生长的抑制作用 血卟啉衍生物可被红光激活而导致 彻底根除小鼠和大鼠乳腺肿瘤。 孟加拉玫瑰是一种已被详细研究过的黄杂环烯类染料 用脖子。它是在许多情况下形成单线态氧的有用增敏剂 不同的溶剂和分子形式，包括聚合的。它的 结构可以很容易地修改，结构变化几乎不会引起变化 在光化学或光物理特性方面。这是这样做的一个目的 建议进一步发展这种染料的化学，它最像 染料，是非常复杂的。我们打算让它成为典型的染料 用于未来染料改性和化学处理的系统 光疗法的应用可以基于。 我们的意图是通过适当的结构修改来证明 该增感剂可以针对特定的可氧化底物来 提高特定配对分子的氧化选择性，以及 使用这种靶向光敏剂概念来改变，和 从这些氧化过程中获得的产品。我们称这为 靶向光动力作用原理。4岁的罗斯·孟加拉将成为 功能化以与酶和抗体反应，这些将被使用 为了选择性地吸引诸如底物的其他分子实体， 抑制剂或抗原。这应该会吸引这些后一种实体到 致敏剂功能化的酶或抗体的位置，从而对 单线态氧的来源。它应该会提高局部集中度 源附近的潜在单线态氧受体-The 增感剂。我们打算应用这一原则，有针对性地进行光动力学 行动，在肿瘤光疗中。协作安排为%1。 Dougherty(光动力疗法)，C.W.Lin(膀胱癌光疗法)， 和J.Spikes(将Xanthene染料掺入脂质体)和A.Oseroff (功能化的单抗)。