Synthesis, characterization, and photodynamic therapy activity of 5,10,15, 20-Tetrakis(carboxyl)porphyrin
Synthesis, characterization, and photodynamic therapy activity of 5,10,15, 20-Tetrakis(carboxyl)porphyrin
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5,10,15,20-四(羧基)卟啉的合成、表征和光动力治疗活性
DOI：
10.1016/j.bmc.2019.03.051
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发表时间：
2019
影响因子：
3.5
通讯作者：
Zhang Hai-Tao
中科院分区：
文献类型：
--
作者：
Zhang Zhao;Yu Hua-Jun;Wu Shang;Huang Hui;Si Li-Ping;Liu Hai-Yang;Shi Lei;Zhang Hai-Tao
水溶性卟啉被认为是光动力学治疗（PDT）的有前途的候选药物。本文研究了一种新型水溶性阴离子卟啉（1-Zn）的光动力学活性。以mTHPC为阳性对照，MTT法检测1-Zn的光动力学抗癌活性。通过荧光显微镜测定细胞分布。在1-Zn处理后用HoloMonitor™ M3仪器记录全息和相衬图像。流式细胞术和荧光显微镜观察诱导凋亡对A549细胞生长的抑制作用。彗星试验检测DNA损伤。免疫印迹法检测凋亡相关蛋白的表达。1-Zn对A549细胞的光毒性作用优于HeLa和HepG 2细胞。有趣的是，1-Zn几乎完全位于细胞质区/细胞器中。1-Zn处理组和单纯光处理组晚期凋亡细胞数均低于1.0%，而1-Zn处理组和照射组晚期凋亡细胞数增加至40.5%（P < 0.05），照射后1-Zn引起细胞内活性氧的产生，导致Δ λ m断裂（P < 0.01）和DNA损伤，1-Zn通过线粒体凋亡途径诱导A549细胞凋亡。此外，1-Zn通过π-π堆积和氢键作用以外结合方式结合在DNA的凹槽中，具有良好的光核酸酶活性，可能作为肺癌细胞的光敏剂。
Water-soluble porphyrins are considered promising drug candidates for photodynamic therapy (PDT). This study investigated the PDT activity of a new water-soluble, anionic porphyrin (1-Zn), which possesses four negative charges. The photodynamic anticancer activity of1-Znwas investigated by the MTT assay, with mTHPC as a positive control. The cellular distribution was determined by fluorescence microscopy. Holographic and phase contrast images were recorded after1-Zntreatment with a HoloMonitor™ M3 instrument. The inhibition of A549 cell growth achieved by inducing apoptosis was investigated by flow cytometry and fluorescence microscopy. DNA damage was investigated by the comet assay. The expression of apoptosis-related proteins was also measured by western blot assays.1-Znhad better phototoxicity against A549 cells than HeLa and HepG2 cancer cells. Interestingly,1-Znwas clearly located almost entirely in the cell cytoplasmic region/organelles. The late apoptotic population was less than 1.0% at baseline in the untreated and only light-treated cells and increased to 40.5% after1-Zntreatment and irradiation (P < 0.05).1-Zntriggered significant ROS generation after irradiation, causing ΔΨm disruption (P < 0.01) and DNA damage.1-Zninduced A549 cell apoptosis via the mitochondrial apoptosis pathway. In addition,1-Znbound in the groove of DNA via an outside binding mode by pi-pi stacking and hydrogen bonding.1-Znexhibits good photonuclease activity and might serve as a potential photosensitizer (PS) for lung cancer cells.