Excellent antitumor effects for gastrointestinal cancers using photodynamic therapy with a novel glucose conjugated chlorin e6
Excellent antitumor effects for gastrointestinal cancers using photodynamic therapy with a novel glucose conjugated chlorin e6
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DOI：
10.1016/j.bbrc.2018.01.171
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发表时间：
2018-02-19
影响因子：
3.1
通讯作者：
Joh, Takashi
中科院分区：
文献类型：
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作者：
Nishie, Hirotada;Kataoka, Hiromi;Joh, Takashi
背景资料：光动力疗法（PDT）利用光敏剂与照射光之间的反应来在癌细胞中产生潜在治疗活性氧物质，例如单线态氧。我们已经报道了几种糖结合二氢卟酚，其在PDT中表现出比日本临床上使用的第二代光敏剂他拉泊芬钠（TS）更强的抗肿瘤作用。本研究以葡萄糖为光敏剂，合成了一种新型的葡萄糖偶联二氢卟酚e6（G-chlorin e6），并对其抗肿瘤活性进行了评价。我们测量了半最大抑制浓度（IC 50）以比较G-二氢卟酚e6和TS的PDT效应，并通过流式细胞术检测G-二氢卟酚e6在癌细胞中的积累。我们还比较了正常永生化食管上皮细胞和食管癌细胞之间的G-二氢卟酚e6的积累。结果：G-chlorin e6 PDT的体外抗肿瘤作用是TS的9000 ~ 34000倍，流式细胞仪检测G-chlorin e6的蓄积量是TS的70-190倍。G-二氢卟酚e6积累更多的选择性食管癌细胞比在食管永生化上皮细胞，并在同种异体移植模型中，PDT与G-二氢卟酚e6表现出非常强的抗肿瘤作用和40%的完全反应（CR）率。结论：G-二氢卟酚e6表现出良好的肿瘤选择性，PDT使用G-二氢卟酚e6显示出最强的抗肿瘤作用之间的所有糖共轭二氢卟酚，我们已经研究。G-chlorin e6被认为是下一代PDT的最佳光敏剂。(C)2018爱思唯尔公司All rights reserved.
Background: Photodynamic therapy (PDT) exploits the reaction between photosensitizer and irradiated light to generate potentially therapeutic reactive oxygen species such as singlet oxygen in cancer cells. We have reported several sugar-conjugated chlorins that express stronger antitumor effects in PDT than talaporfin sodium (TS), a second-generation photosensitizer clinically used in Japan. In this study, we developed a novel glucose-conjugated chlorin e6 (G-chlorin e6) and evaluated its antitumor effects.Methods: G-chlorin e6 was synthesized with a core photosensitizer chlorin e6 conjugated to glucose. We measured the half maximal inhibitory concentration (IC50) to compare the PDT effects of G-chlorin e6 and TS, and flow cytometry was performed to examine the accumulation of G-chlorin e6 in cancer cells. We also compared the accumulation of G-chlorin e6 between normal immortalized esophageal epithelial cells and esophageal cancer cells. Antitumor effects of G-chlorin e6 PDT were finally analyzed in allograft tumor mouse models.Results: PDT in vitro using G-chlorin e6 elicited 9, 000-34,000 times stronger antitumor effects than TS, and there was 70-190 times more G-chlorin e6 accumulated than TS by flow cytometry. G-chlorin e6 accumulated more selectively in esophageal cancer cells than in esophageal immortalized epithelial cells, and in an allograft model, PDT with G-chlorin e6 showed very strong antitumor effects and a 40% complete response (CR) rate.Conclusions: G-chlorin e6 showed excellent tumor selectivity, and PDT using G-chlorin e6 revealed the strongest anti-tumor effects among all sugar-conjugated chlorins that we have studied. G-chlorin e6 is considered to be the best photosensitizer for next-generation PDT. (C) 2018 Elsevier Inc. All rights reserved.