title: Zinc phthalocyanine conjugated with the amino-terminal fragment of urokinase for tumor-targeting photodynamic therapy.
abstract: Photodynamic therapy (PDT) has attracted much interest for the treatment of cancer due to the increased incidence of multidrug resistance and systemic toxicity in conventional chemotherapy. Phthalocyanine (Pc) is one of main classes of photosensitizers for PDT and possesses optimal photophysical and photochemical properties. A higher specificity can ideally be achieved when Pcs are targeted towards tumor-specific receptors, which may also facilitate specific drug delivery. Herein, we develop a simple and unique strategy to prepare a hydrophilic tumor-targeting photosensitizer ATF-ZnPc by covalently coupling zinc phthalocyanine (ZnPc) to the amino-terminal fragment (ATF) of urokinase-type plasminogen activator (uPA), a fragment responsible for uPA receptor (uPAR, a biomarker overexpressed in cancer cells), through the carboxyl groups of ATF. We demonstrate the high efficacy of this tumor-targeting PDT agent for the inhibition of tumor growth both in vitro and in vivo. Our in vivo optical imaging results using H22 tumor-bearing mice show clearly the selective accumulation of ATF-ZnPc in tumor region, thereby revealing the great potential of ATF-ZnPc for clinical applications such as cancer detection and guidance of tumor resection in addition to photodynamic treatment.
authors: State Key Laboratory of Structural Chemistry, Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, People's Republic of China. Electronic address: zchen@fjirsm.ac.cn.
authors: Zhuo
authors: Z
authors: Chen
authors: State Key Laboratory of Structural Chemistry, Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, People's Republic of China.
authors: Peng
authors: P
authors: Xu
authors: State Key Laboratory of Structural Chemistry, Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, People's Republic of China.
authors: Jincan
authors: J
authors: Chen
authors: State Key Laboratory of Structural Chemistry, Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, People's Republic of China.
authors: Hongwei
authors: H
authors: Chen
authors: State Key Laboratory of Structural Chemistry, Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, People's Republic of China.
authors: Ping
authors: P
authors: Hu
authors: Key Laboratory of Optoelectronic Materials Chemistry and Physics, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, People's Republic of China.
authors: Xueyuan
authors: X
authors: Chen
authors: Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors: Lin
authors: L
authors: Lin
authors: Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350108, People's Republic of China.
authors: Yunmei
authors: Y
authors: Huang
authors: College of Chemistry and Chemical Engineering, Fuzhou University, Fujian 350108, People's Republic of China.
authors: Ke
authors: K
authors: Zheng
authors: State Key Laboratory of Structural Chemistry, Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, People's Republic of China.
authors: Shanyong
authors: S
authors: Zhou
authors: State Key Laboratory of Structural Chemistry, Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, People's Republic of China.
authors: Rui
authors: R
authors: Li
authors: State Key Laboratory of Structural Chemistry, Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, People's Republic of China.
authors: Song
authors: S
authors: Chen
authors: College of Chemistry and Chemical Engineering, Fuzhou University, Fujian 350108, People's Republic of China.
authors: Jianyong
authors: J
authors: Liu
authors: College of Chemistry and Chemical Engineering, Fuzhou University, Fujian 350108, People's Republic of China.
authors: Jinping
authors: J
authors: Xue
authors: State Key Laboratory of Structural Chemistry, Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, People's Republic of China; College of Chemistry and Chemical Engineering, Fuzhou University, Fujian 350108, People's Republic of China. Electronic address: mhuang@fjirsm.ac.cn.
authors: Mingdong
authors: M
authors: Huang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000819:agonists / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D054833:Isoindoles; D051379:Mice; D009363:Neoplasm Proteins / Q000819:agonists / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010778:Photochemotherapy; D055293:Receptors, Urokinase Plasminogen Activator / Q000819:agonists / Q000378:metabolism; D020298:U937 Cells; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D015032:Zinc
chemical_list: D014408:Biomarkers, Tumor; D007211:Indoles; D054833:Isoindoles; D009363:Neoplasm Proteins; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D015032:Zinc; C013647:phthalocyanine
keywords: Photosensitizer; Tumor-imaging; Tumor-targeting; Zinc phthalocyanine