A tumor-targeted activatable phthalocyanine-tetrapeptide-doxorubicin conjugate for synergistic chemo-photodynamic therapy

被引：67

作者：

Ke, Mei-Rong ^{[1
]}

Chen, Shao-Fang ^{[1
]}

Peng, Xiao-Hui ^{[1
]}

Zheng, Qiao-Feng ^{[1
]}

Zheng, Bi-Yuan ^{[1
]}

Yeh, Chih-Kuang ^{[2
]}

Huang, Jian-Dong ^{[1
]}

机构：

[1] Fuzhou Univ, Coll Chem, State Key Lab Photocatalysis Energy & Environm, Fuzhou 350116, Peoples R China

[2] Natl Tsing Hua Univ, Dept Biomed Engn & Environm Sci, Hsinchu 30013, Taiwan

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 127卷

基金：

中国国家自然科学基金;

关键词：

Cancer; Prodrugs; Chemo-photodynamic therapy; Doxorubicin; Phthalocyanine; Fibroblast activation protein; STROMAL FIBROBLASTS; ZINC(II) PHTHALOCYANINE; COMBINATION THERAPY; SINGLET OXYGEN; CANCER-THERAPY; DRUG-DELIVERY; PROTEIN; PHOTOSENSITIZERS; EXPRESSION; NANORODS;

D O I：

10.1016/j.ejmech.2016.12.056

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：200 / 209

页数：10

共 43 条

[1] Stromal fibroblasts in cancer initiation and progression [J].