title: A tumor-targeted activatable phthalocyanine-tetrapeptide-doxorubicin conjugate for synergistic chemo-photodynamic therapy.
abstract: 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.
authors.affiliation: College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350116, China.
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Ke
authors.affiliation: College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350116, China.
authors.forename: Shao-Fang
authors.initials: SF
authors.lastname: Chen
authors.affiliation: College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350116, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Peng
authors.affiliation: College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350116, China.
authors.forename: Qiao-Feng
authors.initials: QF
authors.lastname: Zheng
authors.affiliation: College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350116, China.
authors.forename: Bi-Yuan
authors.initials: BY
authors.lastname: Zheng
authors.affiliation: Department of Biomedical Engineering and Environmental Science, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Yeh
authors.affiliation: College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350116, China. Electronic address: jdhuang@fzu.edu.cn.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004317:Doxorubicin / Q000737:chemistry*; D004357:Drug Synergism; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D054833:Isoindoles; D051379:Mice; D058990:Molecular Targeted Therapy; D009842:Oligopeptides / Q000737:chemistry*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D007211:Indoles; D054833:Isoindoles; D009842:Oligopeptides; D017319:Photosensitizing Agents; D004317:Doxorubicin; C013647:phthalocyanine
keywords: Cancer; Chemo-photodynamic therapy; Doxorubicin; Fibroblast activation protein; Phthalocyanine; Prodrugs