PORPHYRIN PHOTOSENSITIZATION AND PHOTOTHERAPY

光动力学疗法（photodynamic therapy，PDT）治疗肿瘤是一种新的治疗手段 目前正在进行深入研究。 PDT的主要局限性是 持续的皮肤光敏化，沿着需要照射， 630 nm，这是激光技术难以实现的波长。 这 本研究旨在研究新的光敏染料， 二聚体结构，其有助于通过HPD进行肿瘤定位， 目前的临床致敏剂，但有改变，旨在促进 在波长大于750 nm处的吸光度。 这些特工将 由Dr. C.K.昌 评价 毒性和光动力作用位点的研究将由Dr. 亨德森。 直接肿瘤杀伤与间接毒性之间的描述 会造成血管损伤 PDT有效性的决定因素将 可以在体内和体外测定。 我们将描述染料 聚集、疏水性、对不同血浆宏的亲和力， 分子，染料结合位点的环境性质和性质 光损伤。 致敏物在血浆蛋白和血浆中的分布 脂蛋白将通过密度梯度超离心法检测， 使用荧光、吸光度和（可行时）放射性， 定量染料浓度。 新染料的相对有效性 我们应该能够识别这些 预测上级定位和光敏化的试剂 行为 探索这些结构-活性关系是 有望促进用于光动力疗法的新染料的设计。 理解选择性定位的决定因素， 光敏化将对我们的知识做出有益的贡献 肿瘤细胞生物学。

Photodynamic therapy (PDT) of neoplastic disease is a new modality currently undergoing intensive study. The major limitations of PDT are persistent skin photosensization, along with the need for irradiation at 630 nm, a wavelength difficult to achieve by laser technology. This study is designed to examine new photosensitizing dyes based on the dimeric structure which contributes to the tumor-localization by HPD, the current clinical sensitizer, but with alterations designed to promote absorbance at wavelengths greater than 750 nm. These agents will be prepared and chemically characterized by Dr. C.K. Chang. Evaluation of toxicity and of sites of photodynamic action will be carried out by Dr. Henderson. A delineation between direct tumor kill vs. indirect toxicity via vascular damage will be made. Determinants of PDT effectiveness will be determined in vivo and in vitro. We will characterize dye aggregation, hydrophobicity, affinity for different plasma macro- molecules, environmental properties of dye-binding sites and the nature of photodamage. The distribution of sensitizers among plasma protein and lipoproteins will be examined by density-gradient ultracentrifugation, with fluorescence, absorbance and (where feasible) radioactivity used to quantitate dye concentration. As the relative effectiveness of new dyes becomes established, we should be able to identify properties of these agents that predict for superior localizing and photosensitizing behavior. Exploration of these structure-activity relationships is expected to facilitate the design of new dyes for photodynamic therapy. An understanding of the determinants of selective localization and photosensitization will represent a useful contribution to our knowledge of tumor cell biology.