Zhang Feng-Ling, Song Mei-Ru, Yuan Gan-Kun, Ye Huan-Nian, Tian Ye, Huang Ming-Dong, Xue Jin-Ping, Zhang Zhi-Hong, Liu Jian-Yong
State Key Laboratory of Photocatalysis on Energy and Environment & Fujian Engineering Research Center of Functional Materials, College of Chemistry, Fuzhou University , 2 Xueyuan Road, University Town, Fuzhou 350108, Fujian, P. R. China.
College of Pharmaceutical Science, Zhejiang Chinese Medical University , 548 Binwen Road, Hangzhou, 310053, P. R. China.
J Med Chem. 2017 Aug 10;60(15):6693-6703. doi: 10.1021/acs.jmedchem.7b00682. Epub 2017 Jul 24.
The combination of photodynamic therapy and other cancer treatment modalities is a promising strategy to enhance therapeutic efficacy and reduce side effects. In this study, a tamoxifen-zinc(II) phthalocyanine conjugate linked by a triethylene glycol chain has been synthesized and characterized. Having tamoxifen as the targeting moiety, the conjugate shows high specific affinity to MCF-7 breast cancer cells overexpressed estrogen receptors (ERs) and tumor tissues, therefore leading to a cytotoxic effect in the dark due to the cytostatic tamoxifen moiety, and a high photocytotoxicity due to the photosensitizing phthalocyanine unit against the MCF-7 cancer cells. The high photodynamic activity of the conjugate can be attributed to its high cellular uptake and efficiency in generating intracellular reactive oxygen species. Upon addition of exogenous 17β-estradiol as an ER inhibitor, the cellular uptake and photocytotoxicity of the conjugate are reduced significantly. As shown by confocal microscopy, the conjugate is preferentially localized in the lysosomes of the MCF-7 cells.
光动力疗法与其他癌症治疗方式相结合是一种提高治疗效果并减少副作用的有前景的策略。在本研究中，已合成并表征了一种通过三甘醇链连接的他莫昔芬 - 锌（II）酞菁共轭物。该共轭物以他莫昔芬作为靶向部分，对过表达雌激素受体（ERs）的MCF - 7乳腺癌细胞和肿瘤组织具有高特异性亲和力，因此由于具有细胞生长抑制作用的他莫昔芬部分而在黑暗中产生细胞毒性作用，并且由于光敏酞菁单元对MCF - 7癌细胞具有高光细胞毒性。该共轭物的高光动力活性可归因于其高细胞摄取率和产生细胞内活性氧的效率。加入外源性17β - 雌二醇作为ER抑制剂后，共轭物的细胞摄取和光细胞毒性显著降低。共聚焦显微镜显示，该共轭物优先定位于MCF - 7细胞的溶酶体中。
