LIPOSOME AND BSO ENHANCEMENT OF PHOTODYNAMIC THERAPY

脂质体和 BSO 增强光动力治疗

• 批准号: 6563817
• 负责人: MICHAEL CHOPP
• 金额: $ 22.84万
• 依托单位: HEALTHONE ALLIANCE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6563817
• 关键词: biophysics; brain neoplasms; buthionine sulfoximine; cellular pathology; cytotoxicity; drug delivery systems; fluorimetry; glioma; glutathione; histopathology; laboratory rat; liposomes; neoplasm /cancer photoradiation therapy; nonhuman therapy evaluation; pharmacokinetics; photosensitizing agents; radiation therapy dosage; sarcoma; statistics /biometry

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.

这项建议的目的，是加强治疗脑 肿瘤PDT 我们已经确定了两种方法来提高疗效 PDT相对于正常脑选择性地杀死脑肿瘤。 包封在脂质体中的Photofrin和Photofrin 与丁硫克百威亚砜（BSO）（a 谷胱甘肽抑制剂）显著增加PDT毒性， 肿瘤细胞 在这个项目中，我们将开发，实施和优化 这些增强脑肿瘤PDT的con-PDT治疗方法， 研究负责这种治疗的生物物理机制 增强 目的A：测量治疗效果的相对增加， 光动力学疗法治疗大鼠实验性脑肿瘤 Photofrin包封在脂质体中（Photofrin-脂质体）， 与葡萄糖载体中的Photofrin相比的光敏剂 （Photofrin-葡萄糖）作为光敏剂。 假设A：PDT治疗脑肿瘤的增强作用 与Photofrin-葡萄糖相比， 归因于药代动力学和细胞内 Photofrin的定位。 目的B：测量治疗效果的相对增加， 光动力学疗法治疗大鼠实验性脑肿瘤 Photofrin通过使用丁硫基亚砜（BSO）作为PDT的佐剂。 假设B：BSO给药降低了谷氨酰胺水平 在脑肿瘤组织中， 用PDT破坏肿瘤。 我们期望这些增强PDT的方法的优化 脑肿瘤的破坏将在临床上得到应用， 直接增强人类脑肿瘤治疗。