PDT--MECHANISMS AND STRATEGIES FOR OPTIMIZATION

本项目的长期总体目标是提高 了解光敏剂的结构-活性关系， 阴离子和阳离子，用于光动力疗法，以及体外和体内 其作用的体内机制。 所得到的机械信息将 用于制定战略，以提高 光动力/光化学疗法。 这将通过以下方式实现： 以下个人研究项目： 1.具有特定增量结构变化的新型阴离子光敏剂 长波长吸收光敏剂的合成和制备 提供给其他项目。 这些物质的物理性质 将确定致敏剂，并提出比较致敏剂的概念 将提高效率。 2.新型光敏剂的结构/活性关系将在 根据肿瘤细胞和血管的决定因素定义 光敏化 肿瘤灌注与孔内细胞的光敏性 并评估灌注不良的肿瘤区域。 局部和全身 宿主对光敏剂和光动力学处理反应机制将 被研究。 3.新型阳离子光敏剂的合成及结构活性研究 体外和体内机制的关系和机制 将定义光毒性。 多药治疗和联合治疗 我们会设计治疗方法以加强光化学疗法的功效。 4.人肿瘤光动力学治疗反应的动力学研究 将进行研究，包括致敏剂摄取、血管造影时间范围 反应，光漂白和以前的治疗效果。 个人研究项目将得到两个非常重要的支持 技术核心组件--一个用于药物评价和流式细胞术， 一个用于光学方面的研究和非侵入性监测， 治疗进展。 这些对于确保总体进展至关重要， 生产力 生物数学和管理核心组件完成 这个多学科的项目。

It is the long term, overall goal of this Program Project to increase the understanding of structure-activity relationships of photosensitizers, both anionic and cationic, used in photodynamic therapy, and the in vitro and in vivo mechanisms of their action. The mechanistic information derived will be used to devise strategies to improve the efficacy of photodynamic/photochemotherapy. This will be achieved through the following Individual Research Projects: 1. New anionic photosensitizers of specific incremental structural changes and long-wavelength absorbing photosensitizers will be synthesized and made available to other projects. The photophysical properties of these sensitizers will be determined and a concept for comparison of sensitizer efficiency will be developed. 2. Structure/activity relationships of novel photosensitizers will be defined with regard to the determinants for tumor cell and vascular photosensitization. Tumor perfusion and photosensitivity of cells in well and poorly perfused tumor regions will be assessed. Local and systemic host response mechanisms to photosensitizer and photodynamic treatment will be studied. 3. New cationic photosensitizers will be synthesized and structure-activity relationships and mechanisms of in vitro and in vivo mechanisms of phototoxicity will be defined. Multiagent treatments and combination treatments will be devised to enhance the efficacy of photochemotherapy. 4. The dynamics of the response to photodynamic therapy of human tumors will be studied, including sensitizer uptake, time frame of vascular response, photobleaching and effects of previous treatments. The Individual Research Projects will be supported by two very important technical core components -- one for drug evaluation and flow cytometry, one for optical aspects of the research and non-invasive monitoring of treatment progress. These are critical to ensure overall progress and productivity. Biomathematics and administrative core components complete this multi-disciplinary Program Project.