SUBCELL LOCALIZATION OF BPD MA IN ADHERENT CELLS UTILIZING TWO PHOTON MICROSCOPY

利用两个光子显微镜对贴壁细胞中的 BPD MA 进行亚细胞定位

• 批准号: 6121907
• 负责人: MICHAEL G NICHOLS
• 金额: $ 0.22万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6121907
• 关键词: animal tissue; bioengineering /biomedical engineering; biological products; biomedical resource; lasers

We propose to evaluate two-photon microscopy of BPD-MA to study subcellular localization under a variety of conditions. Benzoporphyrin Derivative is a second-generation photosensitizing compound currently undergoing phase II clinical trials for use in treating psoriasis, age-related macular degeneration as well as cutaneous oncology. Previous research has demonstrated that this drug is a potent sensitizer, with efficacy in cell killing demonstrated at concentrations below 200 ng/ml. Its primary subcellular target is believed to the mitochondria, where it has been demonstrated that BPD-MA can photodynamically uncouple oxidative phosphorylation in the isolated rat mitochondria. Our initial experiments have sought to optimize two-photon microscopy for observation of this drug. The two-photon cross section of BPD-MA in a liposomal preparation has recently been measured from 820-980 nm. Having measured the cross section, we will be able to evaluate a detection threshold that will then be ve rified in adherent cell culture. Organelle localization studies have been outlined are expected to proceed in the near future.

我们建议评估双光子显微镜的BPD-MA研究 在各种条件下的亚细胞定位。 苯并卟啉衍生物是第二代光敏剂 目前正在进行II期临床试验的化合物， 治疗牛皮癣、老年性黄斑变性以及 皮肤肿瘤学 此前的研究表明，这种药物 是一种有效的致敏剂，在细胞杀伤方面的功效在 浓度低于200 ng/ml。 它的主要亚细胞靶点是 据信是线粒体，在那里已经证明， BPD-MA可以光动力学解偶联氧化磷酸化， 分离的大鼠线粒体。 我们最初的实验试图 优化双光子显微镜观察这种药物。 的 脂质体制剂中BPD-MA的双光子截面 最近从820-980 nm测量。 测量了十字架 部分，我们将能够评估一个检测阈值， 然后在贴壁细胞培养中鉴定。 细胞器定位 预计在不久的将来将进行研究。