Metallation of pentaphyrin with Lu(III) dramatically increases reactive-oxygen species production and cell phototoxicity

Photodynamic therapy (PDT) is an emerging cancer treatment modality based on the excitation of a nontoxic photosensitizer with harmless visible light to produce reactive-oxygen species (ROS) that induce apoptosis and/or necrosis in cancer cells. As the efficacy of this therapy strongly depends of the nature of the photosensitizer, there is a great interest to develop new photoactive molecules. Here we report for the first time the synthesis, characterization and bioactivity of metal complexes between the non-aromatic expanded porphyrin, namely 20-[[4′-(Trimethylsilyl)ethoxycarbonyl]phenyl-2,13-dimethyl-3,12-diethyl-[24] iso-pentaphyrin (PCRed) and Zn(II) [Zn(II)-PCRed] or Lu(III) [Lu(III)-PCRed]. The complexation of these two diamagnetic heavy metal ions to PCRed improved the properties of the free photosensitizer as a PDT drug. We discovered that the 1:1 complex between PCRed and Lu(III) significantly increases the cellular uptake, ROS production and antiproliferative capacity in four cancer cell lines. Our study shows that metal complexation is a useful strategy to potentiate iso-pentaphyrin as a PDT drug.     

陈士铎辨治痿症临证经验和特色探析

[目的]探析陈士铎治痿经验及用药特色，以期为痿症的临床辨治提供新思路。[方法]通过研习《辨证录》痿症门的八则医案，并借助《石室秘录》及《本草新编》中有关痿症的方药论述加以理解分析，从而总结归纳陈士铎对痿症的分类、病因病机、治则治法及方药配伍等方面的经验特色。[结果]陈士铎将痿症分为五痿，分属五脏，医案详症略脉，重视从症状入手定位病脏。病因首推阳明胃火，五脏痿症因脏腑相关及五行生克特点而病机各异，但本质皆为肾水不足，骨空无髓。临床治疗上，陈氏主张从胃肾出发，遵循泻胃火、滋肾水，兼顾他脏的原则，强调忌大寒泻火，宜微寒散火，同时大补肾阴、和调脏腑。用药上，陈氏重用玄参、麦冬为君，配以熟地黄，并善用甘菊花清退胃火。[结论]陈士铎诊治痿症多有效验，并极具个人特色，在汲取前人思想精华的基础上，常有自己的新见解，值得后世借鉴与参考。