A tumor-targeted activatable phthalocyanine-tetrapeptide-doxorubicin conjugate for synergistic chemo-photodynamic therapy
A tumor-targeted activatable phthalocyanine-tetrapeptide-doxorubicin conjugate for synergistic chemo-photodynamic therapy
复制标题
用于协同化学光动力治疗的肿瘤靶向可激活酞菁-四肽-阿霉素缀合物
DOI：
10.1016/j.ejmech.2016.12.056
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发表时间：
2017-02-15
影响因子：
6.7
通讯作者：
Huang, Jian-Dong
中科院分区：
文献类型：
--
作者：
Ke, Mei-Rong;Chen, Shao-Fang;Huang, Jian-Dong
化学光动力疗法是一种很有前途的癌症治疗策略。然而，如何开发一种副作用小、靶向性高、同时具有高效协同效应的化学光动力治疗药物仍然是一个挑战。在此，我们报告了一个锌（II）酞菁（ZnPc）-阿霉素（DOX）前药连接成纤维细胞活化蛋白（FAP）响应短肽与序列的Thr-Ser-Gly-Pro的化学光动力治疗。偶联物对ZnPc的光敏活性和DOX的细胞毒性均有明显的抑制作用。然而，FAP触发的光敏剂和DOX的分离可以显著增强荧光发射、单线态氧产生、暗细胞毒性和光细胞毒性，并导致针对HepG 2细胞的协同抗癌功效。该前体药物在小鼠肿瘤组织中也能特异有效地活化。因此，这种前药在化学光动力学治疗中显示出巨大的临床应用潜力。(C)2016 Elsevier Masson SAS。All rights reserved.
Chemo-photodynamic therapy is a promising strategy for cancer treatments. However, it remains a challenge to develop a chemo-photodynamic therapeutic agent with little side effect, high tumor-targeting, and efficient synergistic effect simultaneously. Herein, we report a zinc(II) phthalocyanine (ZnPc)-doxorubicin (DOX) prodrug linked with a fibroblast activation protein (FAP)-responsive short peptide with the sequence of Thr-Ser-Gly-Pro for chemo-photodynamic therapy. In the conjugate, both photosensitizing activity of ZnPc and cytotoxicity of DOX are inhibited obviously. However, FAP-triggered separation of the photosensitizer and DOX can enhance fluorescence emission, singlet oxygen generation, dark- and photo-cytotoxicity significantly, and lead to a synergistic anticancer efficacy against HepG2 cells. The prodrug can also be specifically and efficiently activated in tumor tissue of mice. Thus, this prodrug shows great potential for clinical application in chemo-photodynamic therapy. (C) 2016 Elsevier Masson SAS. All rights reserved.