Shinoda Yo, Takahashi Tsutomu, Akimoto Jiro, Ichikawa Megumi, Yamazaki Hiromi, Narumi Atsushi, Yano Shigenobu, Fujiwara Yasuyuki
Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.
J Toxicol Sci. 2017;42(1):111-119. doi: 10.2131/jts.42.111.
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, β-mannose-conjugated chlorin (β-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 β-M-chlorin in human-derived cell lines, and β-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 photosensitizers, 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.
光动力疗法（PDT）是一种经美国食品药品监督管理局批准的癌症治疗方法，它利用光敏剂和激光照射产生活性氧，从而诱导肿瘤细胞死亡。光敏剂已从第一代逐步发展到第三代，在细胞特异性、副作用和毒性降低、对照射的敏感性增加以及光敏剂在健康细胞中的持久性降低等方面都有改进。这些改进是通过使用细胞系对当前和新型光敏剂进行基础对比实验实现的；然而，由于光敏剂可能具有细胞类型特异性，因此应仔细评估。在本研究中，我们使用七种不同的大鼠和人类细胞系以及从大鼠胚胎制备的神经元/胶质原代培养物，将第三代光敏剂β-甘露糖共轭二氢卟吩（β-M-二氢卟吩）与第二代光敏剂他拉泊芬钠（NPe6）进行了比较。在人源细胞系中，NPe6比β-M-二氢卟吩更有效；在大鼠原代培养物和大鼠源细胞系中，除大鼠嗜铬细胞瘤细胞系PC12外，β-M-二氢卟吩比NPe6更有效。不同细胞类型中光毒性的这些差异并非由于光敏剂之间光敏性的差异，而是与不同细胞类型中不同光敏剂的分布和积累速率有关。这些数据表明，由于每种光敏剂可能具有细胞类型特异性，因此应使用尽可能多的细胞类型对用于光动力疗法（PDT）的光敏剂进行评估。
