Faculty of Science and Technology, University of Silesia, 75. Pułku Piechoty 1A, 41-500, Chorzów, Poland.
Faculty of Science and Technology, University of Silesia, 75. Pułku Piechoty 1A, 41-500, Chorzów, Poland.
Photodiagnosis Photodyn Ther. 2020 Jun;30:101799. doi: 10.1016/j.pdpdt.2020.101799. Epub 2020 May 5.
Many aspects are currently being investigated, with the aim of improving the application of PDT in the clinic by rendering it more effective. One of the current trends focuses on the use of nanocarriers. The aim of this study is to describe novel photosensitizers among polyol amide chlorin e6 derivatives for photodynamic therapy (PDT) using liposomes.
In addition to their intracellular localization and antiproliferative activity against HCT116 cells, appropriate photophysical features have been determined (especially high O quantum yield production).
Fluorescent microscopy demonstrated that the compounds entered the endoplasmic reticulum (ER), lysosomes, mitochondria and partially the cytoplasm. All of the chlorins showed no dark cytotoxicity; however, high phototoxicity was observed. Using optical and electron microscopy, we investigated the impact of chlorin-based PDT upon cell damage leading to cell death. Chl ara 3 was identified as the most promising compound among polyol amide chlorin e6 derivatives and improved phototoxicity was observed as compared with a clinically approved temoporfin. Our results indicate that newly-synthesized chlorins seem to be promising candidates for PDT application, and two of them (chl ara 3 and chl mme 2) may create promising new drugs, both in the form of a free compound and as a liposomal formulation.
目前正在研究许多方面，旨在通过提高 PDT 的疗效来改善其在临床上的应用。当前的一个趋势是关注使用纳米载体。本研究旨在描述新型聚醇酰胺氯 e6 衍生物作为光敏剂的脂质体在光动力疗法（PDT）中的应用。
除了它们在细胞内的定位和对 HCT116 细胞的抗增殖活性外，还确定了适当的光物理特性（特别是高 O 量子产率的产生）。
荧光显微镜显示，这些化合物进入了内质网（ER）、溶酶体、线粒体，并部分进入了细胞质。所有的叶绿素都没有暗毒性；然而，观察到了很高的光毒性。使用光学和电子显微镜，我们研究了基于叶绿素的 PDT 对导致细胞死亡的细胞损伤的影响。Chl ara 3 被确定为聚醇酰胺氯 e6 衍生物中最有前途的化合物，与临床批准的 Temoporfin 相比，观察到了更高的光毒性。我们的结果表明，新合成的叶绿素似乎是 PDT 应用的有前途的候选物，其中两种（Chl ara 3 和 Chl mme 2）可能作为游离化合物和脂质体制剂形成有前途的新药。
