PORPHYRIN PHOTOSENSITIZATION AND PHOTOTHERAPY

光动力疗法(PDT)是治疗肿瘤的一种新方法 目前正在进行密集的研究。PDT的主要局限性是 持续的皮肤光敏化，以及需要照射在 630 nm，这是一个用激光技术很难达到的波长。这 这项研究是为了研究新的光敏染料，基于 有助于HPD定位肿瘤的二聚体结构， 目前的临床敏感剂，但经过修改旨在促进 波长大于750 nm的吸光度。这些特工将会是 由张启坤博士制备并进行了化学表征。评估 毒性和光动力作用部位的研究将由Dr。 亨德森。直接杀伤肿瘤与间接毒性之间的界限 会造成血管损伤。光动力疗法有效性的决定因素是 在体内和体外均可测定。我们将对染料进行表征 不同大分子血浆的聚集性、疏水性、亲和力 染料结合部位的分子、环境性质和性质 光损伤。致敏剂在血浆蛋白和血浆中的分布 脂蛋白将通过密度梯度超速离心法进行检测， 使用荧光、吸光度和(在可行的情况下)放射性 量化染料浓度。作为新染料的相对有效性 变得确定，我们应该能够识别这些 预测卓越的定位和光敏作用的药物 行为。对这些结构-活性关系的探索是 期望为光动力疗法的新染料的设计提供便利。 了解选择性本地化的决定因素和 光敏化将对我们的知识做出有益的贡献 肿瘤细胞生物学的研究。

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.