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TARGETED PHOTODYNAMIC ACTION

定向光动力作用

基本信息

批准号：
3179081
负责人：
DOUGLAS C NECKERS
金额：
$ 8.5万
依托单位：
BOWLING GREEN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-04-01 至 1990-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3179081
关键词：
breast neoplasms chromophore laboratory mouse laboratory rat ligands monoclonal antibody neoplasm /cancer photoradiation therapy nonvisual photosensitivity respiratory oxygenation

项目摘要

"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).

“光辐射疗法是一种需要使用光敏剂当敏化剂被光子激活时，在光谱的可见光区域。“它最近的使用是由 Doughnard报道荧光素衍生物可以被激活， 488 nm的光，以降低小鼠乳腺的生长速度，血卟啉衍生物可被红光激活，在小鼠和大鼠中完全根除乳腺肿瘤。玫瑰红是一种氧杂蒽染料，其性质已被详细研究关于Neckers 它是一种有用的敏化剂，在许多情况下用于单线态氧的形成。不同的溶剂和分子形式，包括聚合物。其结构易于修改，结构变化引起的变化很小在光化学或光物理特性上。这是一个目的，建议进一步发展这种染料的化学性质，染料，是非常复杂的。我们打算把它变成未来染料改性和化学形成光疗应用可以基于。我们的目的是证明通过适当的结构修饰该敏化剂可被引导至特定的可氧化基质，增加特定配偶体分子氧化的选择性，和使用这种靶向光敏剂概念来改变从这些氧化过程中获得的产物。我们称之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，为了选择性地吸引其它分子实体如底物，抑制剂或抗原。这将吸引这些实体到致敏剂官能化的酶或抗体的位点，并因此至致敏剂官能化的酶或抗体的位点。单线态氧的来源。它应加强当地的集中度，潜在的单线态氧受体在附近的来源- 致敏剂我们打算应用这一原则，靶向光动力学在肿瘤光疗中的作用。合作安排1。 Doughnut（光动力疗法）、C. W. Lin（膀胱癌光疗），和J. Spikes（氧杂蒽染料掺入脂质体），和A.奥塞罗夫（功能化的单克隆抗体）。