Comparative photodynamic therapy cytotoxicity of mannose-conjugated chlorin and talaporfin sodium in cultured human and rat cells
Comparative photodynamic therapy cytotoxicity of mannose-conjugated chlorin and talaporfin sodium in cultured human and rat cells
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DOI：
10.2131/jts.42.111
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发表时间：
2017-02-01
影响因子：
2
通讯作者：
Fujiwara, Yasuyuki
中科院分区：
文献类型：
--
作者：
Shinoda, Yo;Takahashi, Tsutomu;Fujiwara, Yasuyuki
光动力疗法(PDT)是美国食品和药物管理局(FDA)批准的一种治疗癌症的方法，它利用光敏剂和激光照射产生活性氧物种来诱导肿瘤细胞死亡。从第一代到第三代，光敏剂已经逐步发展起来，提高了细胞特异性，减少了副作用和毒性，增加了对辐射的敏感性，减少了光敏剂在健康细胞中的持久性。这些改进是通过使用细胞系的现有光敏剂和新型光敏剂之间的基本比较实验实现的；然而，应该仔细评估光敏剂，因为它们可能具有细胞类型特异性。在这项研究中，我们比较了第三代光敏剂，β-甘露糖结合氯(β-M-氯素)和第二代，他拉普芬钠(NPe6)，使用了七个不同的大鼠和人细胞株，以及从大鼠胚胎制备的神经元/神经胶质原代培养。除大鼠嗜铬细胞瘤细胞系PC12外，NPe6在人源性细胞系中的作用强于βM-氯，在大鼠原代培养和大鼠来源的细胞系中，β-M-氯比NPe6更有效。不同细胞类型的光毒性差异不是由于光敏剂之间的光敏性差异，而是与不同细胞类型中不同的分布和积累速率有关。这些数据表明，对PDT的光敏剂的评价应该使用尽可能多的细胞类型，因为每种光敏剂都可能具有细胞类型特异性。
Photodynamic therapy (PDT) is a Food and Drug Administration authorized method for cancer treatment, which uses photosensitizer and laser photo-irradiation to generate reactive oxygen species to induce cell death in tumors. Photosensitizers have been progressively developed, from first to third generation, with improvements in cell specificity, reduced side effects and toxicity, increased sensitivity for irradiation and reduced persistence of photosensitizer in healthy cells. These improvements have been achieved by basic comparative experiments between current and novel photosensitizers using cell lines; however, photosensitizers should be carefully evaluated because they may have cell type specificity. In the present study, we compared a third-generation photosensitizer, beta-mannose-conjugated chlorin (beta-M-chlorin), with the second generation, talaporfin sodium (NPe6), using seven different rat and human cell lines and a neuronal/glial primary culture prepared from rat embryos. NPe6 was more effective than beta M chlorin in human-derived cell lines, and beta-M-chlorin was more effective than NPe6 in rat primary cultures and rat-derived cell lines, except for the rat pheochromocytoma cell line, PC12. These differences of phototoxicity in different cell types are not because of differences in photosensitivity between the photo sensitizers, but rather are associated with different distribution and accumulation rates in the different cell types. These data suggest that evaluation of photosensitizers for PDT should be carried out using as large a variety of cell types as possible because each photosensitizer may have cell type specificity.