Photodynamic effects of porphyrin and chlorin photosensitizers in human colon adenocarcinoma cells
Photodynamic effects of porphyrin and chlorin photosensitizers in human colon adenocarcinoma cells
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DOI：
10.1016/j.bmc.2004.07.011
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发表时间：
2004-09-15
影响因子：
3.5
通讯作者：
Monti, E
中科院分区：
文献类型：
--
作者：
Banfi, S;Caruso, E;Monti, E
光动力疗法（PDT）是一种癌症治疗方法，涉及肿瘤定位光敏剂的全身管理；当被适当波长的光激活时，它会与分子氧相互作用，形成一种被称为单线态氧的有毒短命物质，这种物质被认为可以介导细胞死亡。Photofrin(R)是卟啉低聚物的复杂混合物，最近已获得FDA批准用于食管癌和支气管内癌的光动力学治疗，但其光动力学和毒性特征远不理想。在本研究中，我们评估了一系列基于卟啉的ps，其中一些是我们小组新合成的，目的是鉴定具有更有利特性的药物。对于卟啉系列中最有效的化合物，还合成了氯的类似物；为了比较，筛选还包括Photofrin(R)。采用MTT法对培养的人结肠腺癌细胞系（HCT116）进行细胞毒性研究；结果表明，3,4,5-三甲氧基苯基、3OH-苯基和4oh -苯基以及磺胺苯基衍生物的效价明显高于Photofrin(R)。流式细胞术和荧光显微镜研究表明，pdt处理的HCT116细胞主要以凋亡方式死亡。综上所述，本研究中描述的新型ps，属于卟啉和氯啉系列，在体外杀死结肠癌细胞方面比Photofrin(R)更有效；将这些观察结果扩展到体内模型，特别是关于更深层次的氯衍生物，可能会导致肿瘤PDT的发展取得重大进展。(C) 2004 Elsevier Ltd.版权所有。
Photodynamic therapy (PDT) is a cancer treatment involving systemic administration of a tumor-localizing photosensitizer; this, when activated by the appropriate wavelength of light, interacts with molecular oxygen to form a toxic, short-lived species known as singlet oxygen, which is thought to mediate cellular death. Photofrin(R) a complex mixture of porphyrin oligomers has recently received FDA approval for the photodynamic treatment of esophageal and endobronchial carcinoma, but its photodynamic and toxicity profiles are far from ideal. In the present study we evaluated a series of porphyrin-based PSs, some of which newly synthesized by our group, with the aim to identify agents with more favorable characteristics. For the most effective compounds in the porphyrin series, chlorin analogs were also synthesized; for comparison, the screening also included Photofrin(R). cytotoxicity studies were performed by the MTT assay on a cultured human colon adenocarcinoma cell line (HCT116); the results indicate that the 3,4,5-trimethoxyphenyl, 3OH- and 4OH-phenyl, and the sulfonamidophenyl derivatives are significantly more potent than Photofrin(R) . Flow cytometric studies and fluorescence microscopy indicate that in PDT-treated HCT116 cells death occurs mainly by apoptosis.In summary, novel PSs described in the present study, belonging both to the porphyrin and chlorin series, have proven more effective than Photofrin(R) in killing colon cancer cells in vitro; extending these observation to in vivo models, particularly regarding the deeper reaching chlorin derivatives, might lead to significant advances in the development of tumor PDT. (C) 2004 Elsevier Ltd. All rights reserved.