LIPOSOME AND BSO ENHANCEMENT OF PHOTODYNAMIC THERAPY

这项建议的目的是加强对脑部疾病的治疗。 肿瘤合并光动力疗法。我们已经确定了两种提高疗效的方法 相对于正常脑组织，光动力疗法选择性地杀伤脑瘤。 光固化磷脂脂质体和光固化磷脂 与丁硫氨酸亚磺酰亚胺(BSO)(A)联用 谷胱甘肽抑制剂)显著增加了对 肿瘤细胞。在这个项目中，我们将开发、实施和优化 这些联合PDT的治疗方法可提高脑肿瘤的PDT和 研究导致这种治疗的生物物理机制 增强功能。 目的A：测量治疗效果的相对增加 光动力疗法对大鼠实验性脑肿瘤的治疗作用 用脂质体(Photofrin-liposome)包裹的光敏蛋白作为 葡萄糖载体中光敏剂与光敏剂的比较 (光敏剂-葡萄糖)作为光敏剂。 假设A：PDT在脑肿瘤治疗中的增强作用 使用Photofrin脂质体与Photofrin-葡萄糖相比 归因于药代动力学和细胞内的改变 感光胶片的本地化。 目的B：测量治疗效果的相对增加 光动力疗法对大鼠实验性脑肿瘤的治疗作用 用丁硫氨酸亚磺酰亚胺(BSO)作为光动力疗法的佐剂。 假设B：服用BSO可降低谷胱甘肽水平 在脑瘤组织中，因此增加了大脑的强度 用光动力疗法破坏肿瘤。 我们期望这些方法的优化能够增强光动力疗法 脑肿瘤毁损术将在临床上得到应用，并可能 人脑肿瘤的直接增强治疗。

The objective of this proposal is to enhance the treatment of brain tumor with PDT. We have identified two methods to increase the efficacy of PDT to selectively kill brain tumor relative to normal brain. Photofrin administered encapsulated in a liposome and photofrin administered in conjunction with buthionine sulfoximide (BSO) (a glutathione inhibitor) significantly increases the PDT toxicity to tumor cells. In this project, we will develop, implement and optimize these con-PDT treatment methods of enhancing the PDT of brain tumor and investigate biophysical mechanisms responsible for this therapeutic enhancement. Aim A: To measure the relative increase in therapeutic efficacy of photodynamic therapy in experimental brain tumor in rat treated with Photofrin encapsulated in a liposome (Photofrin-liposome) as the photosensitizing agent compared to Photofrin in a dextrose vehicle (Photofrin-dextrose) as the photosensitizing agent. Hypothesis A: The enhancement of PDT in the treatment of brain tumor with Photofrin-liposome when compared to Photofrin-dextrose is attributed to alterations of the pharmacokinetics and the intracellular localization of Photofrin. Aim B: To measure the relative increase in therapeutic efficacy of photodynamic therapy in experimental brain tumor in rat treated with Photofrin by using buthionine sulfoximide (BSO) as an adjuvant to PDT. Hypothesis B: Administration of BSO decreases the level of gluthione in brain tumor tissue and therefore augments the intensity of brain tumor destruction with PDT. We expect that the optimization of these methods of enhancement of PDT destruction of brain tumor will find application in the clinic and may direct augmentation of human brain tumor treatment.