A Basic Study of Photodynamic Therapy with Glucose-Conjugated Chlorin e6 Using Mammary Carcinoma Xenografts
A Basic Study of Photodynamic Therapy with Glucose-Conjugated Chlorin e6 Using Mammary Carcinoma Xenografts
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DOI：
10.3390/cancers11050636
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发表时间：
2019-05-01
期刊：
影响因子：
5.2
通讯作者：
Okamoto, Yoshiharu
中科院分区：
文献类型：
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作者：
Osaki, Tomohiro;Hibino, Shota;Okamoto, Yoshiharu
通过利用Warburg效应（肿瘤比正常细胞消耗更高的葡萄糖水平的现象）对癌细胞增强光动力治疗（PDT）的效果，我们开发了一种新的光敏剂，葡萄糖共轭氯e6 （G-Ce6）。我们在体外和体内分析了G-Ce6 PDT对犬乳腺癌（CMC）的治疗效果。研究了G-Ce6在2、5和20 mg/kg时在正常犬体内的药代动力学，并利用CMC细胞（SNP细胞）在体外研究了G-Ce6的细胞内定位、浓度和光动力学效应。G-Ce6 （10 mg/kg）于激光照射前5 min或3 h给药于SNP荷瘤小鼠模型。体外研究表明，G-Ce6主要定位于溶酶体。PDT组细胞活力以G-Ce6浓度和光强度依赖的方式下降。细胞凋亡抑制剂不抑制G-Ce6 PDT诱导的细胞死亡。在体内研究中，间隔5 min的PDT比间隔3 h的PDT表现出更大的效果。g - ce6 （2 mg/kg）的平均最大血药浓度为15.19 +/- 4.44 μ g/mL，半衰期为3.02 +/- 0.58 h。因此，G-Ce6间隔5 min的PDT被认为对CMC有效。
By using the Warburg effect-a phenomenon where tumors consume higher glucose levels than normal cells-on cancer cells to enhance the effect of photodynamic therapy (PDT), we developed a new photosensitizer, glucose-conjugated chlorin e6 (G-Ce6). We analyzed the efficacy of PDT with G-Ce6 against canine mammary carcinoma (CMC) in vitro and in vivo. The pharmacokinetics of G-Ce6 at 2, 5, and 20 mg/kg was examined in normal dogs, whereas its intracellular localization, concentration, and photodynamic effects were investigated in vitro using CMC cells (SNP cells). G-Ce6 (10 mg/kg) was administered in vivo at 5 min or 3 h before laser irradiation to SNP tumor-bearing murine models. The in vitro study revealed that G-Ce6 was mainly localized to the lysosomes. Cell viability decreased in a G-Ce6 concentration- and light intensity-dependent manner in the PDT group. Cell death induced by PDT with G-Ce6 was not inhibited by an apoptosis inhibitor. In the in vivo study, 5-min-interval PDT exhibited greater effects than 3-h-interval PDT. The mean maximum blood concentration and half-life of G-Ce6 (2 mg/kg) were 15.19 +/- 4.44 mu g/mL and 3.02 +/- 0.58 h, respectively. Thus, 5-min-interval PDT with G-Ce6 was considered effective against CMC.