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

我们建议评估BPD-MA的双光子显微镜来研究 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 目前正在进行第二阶段临床试验的化合物用于 治疗银屑病、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 是一种有效的增敏剂，其杀灭细胞的功效在 浓度低于200 ng/ml。它的主要亚细胞靶点是 被认为是线粒体，在那里已经被证明 BPD-MA可以光动力解偶联细胞内的氧化磷酸化 分离大鼠线粒体。我们最初的实验试图 优化双光子显微镜用于该药物的观察。这个 BPD-MA在脂质体中的双光子散射截面 最近测量的波长范围为820-980 nm。量了十字之后 部分中，我们将能够评估检测阈值 然后在贴壁细胞培养中培养。细胞器定位 已概述的研究工作预计将在不久的将来继续进行。

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.