Department of Biochemistry, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, United States of America.
PLoS One. 2017 Dec 4;12(12):e0188535. doi: 10.1371/journal.pone.0188535. eCollection 2017.
Increased interest in clinical application of photodynamic therapy (PDT) in various medical fields poses a demand for better understanding of processes triggered by photo-treatment. Most of the work on PDT performed so far has focused on the immediate effects of photo-treatment. It is generally accepted that cellular damage occurs during light exposure and within a short period thereafter. If cells are not killed during the PDT, they might recover, depending on the extent of the photo-induced damage. Little is known, however, about the relationship between the properties of photosensitizers (PSs) and the delayed consequences of PDT. The aim of this work was to investigate cellular responses to sub-lethal photodynamic treatment and how toxicogenic potency may be affected by molecular features of the PS. Results demonstrated that for cationic porphyrin-based PSs, lipophilicity is the main factor determining the fate of the cells in the 24-hour post-illumination period. PSs with amphiphilic properties initiated oxidative reactions that continued in the dark, long after light exposure, and caused suppression of metabolism and loss of cell viability with concomitant changes in electrophoretic mobility of proteins, including caspases. Apoptotic activity was not stimulated in the post-illumination period. This study demonstrated that in PDT mediated by amphiphilic cationic metalloporphyrin PSs, even when immediate photo-damage is relatively mild, destructive oxidative processes initiated during PDT continue in the absence of light to substantially impair metabolism, and that post-illumination protein modification may modify utilization of cell death pathways.
在各个医学领域，人们对光动力疗法（PDT）的临床应用越来越感兴趣，这对更好地理解光疗引发的过程提出了要求。迄今为止，大多数 PDT 相关工作都集中在光疗的即时效应上。人们普遍认为，细胞损伤发生在光暴露期间及其后的短时间内。如果细胞在 PDT 期间没有被杀死，它们可能会恢复，具体取决于光诱导损伤的程度。然而，关于光敏剂（PS）的特性与 PDT 的延迟后果之间的关系，人们知之甚少。这项工作的目的是研究细胞对亚致死光动力处理的反应，以及毒理学效力如何受到 PS 分子特征的影响。结果表明，对于阳离子卟啉基 PS，亲脂性是决定细胞在光照后 24 小时内命运的主要因素。具有两亲性的 PS 引发了氧化反应，这些反应在光照后很长时间的黑暗中仍在继续，并导致代谢抑制和细胞活力丧失，同时蛋白质的电泳迁移率发生变化，包括半胱天冬酶。在光照后阶段没有刺激细胞凋亡活性。这项研究表明，在由两亲性阳离子金属卟啉 PS 介导的 PDT 中，即使即时光损伤相对较轻，在没有光照的情况下， PDT 中引发的破坏性氧化过程仍会继续，从而大大损害代谢，并且光照后蛋白质修饰可能会改变细胞死亡途径的利用。
