PMID- 24969665 OWN - NLM STAT- MEDLINE DCOM- 20150514 LR - 20211203 IS - 1878-7568 (Electronic) IS - 1742-7061 (Linking) VI - 10 IP - 10 DP - 2014 Oct TI - Zinc phthalocyanine conjugated with the amino-terminal fragment of urokinase for tumor-targeting photodynamic therapy. PG - 4257-68 LID - S1742-7061(14)00282-7 [pii] LID - 10.1016/j.actbio.2014.06.026 [doi] AB - 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. CI - Copyright (c) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. FAU - Chen, Zhuo AU - Chen Z AD - 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. FAU - Xu, Peng AU - Xu P AD - 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. FAU - Chen, Jincan AU - Chen J AD - 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. FAU - Chen, Hongwei AU - Chen H AD - 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. FAU - Hu, Ping AU - Hu P AD - 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. FAU - Chen, Xueyuan AU - Chen X AD - 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. FAU - Lin, Lin AU - Lin L AD - Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. FAU - Huang, Yunmei AU - Huang Y AD - Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350108, People's Republic of China. FAU - Zheng, Ke AU - Zheng K AD - College of Chemistry and Chemical Engineering, Fuzhou University, Fujian 350108, People's Republic of China. FAU - Zhou, Shanyong AU - Zhou S AD - 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. FAU - Li, Rui AU - Li R AD - 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. FAU - Chen, Song AU - Chen S AD - 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. FAU - Liu, Jianyong AU - Liu J AD - College of Chemistry and Chemical Engineering, Fuzhou University, Fujian 350108, People's Republic of China. FAU - Xue, Jinping AU - Xue J AD - College of Chemistry and Chemical Engineering, Fuzhou University, Fujian 350108, People's Republic of China. FAU - Huang, Mingdong AU - Huang M AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140624 PL - England TA - Acta Biomater JT - Acta biomaterialia JID - 101233144 RN - 0 (Biomarkers, Tumor) RN - 0 (Indoles) RN - 0 (Isoindoles) RN - 0 (Neoplasm Proteins) RN - 0 (Receptors, Urokinase Plasminogen Activator) RN - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator) RN - J41CSQ7QDS (Zinc) RN - V5PUF4VLGY (phthalocyanine) SB - IM MH - Animals MH - Biomarkers, Tumor/agonists/metabolism MH - Drug Delivery Systems/*methods MH - Humans MH - Indoles/chemistry/*pharmacology MH - Isoindoles MH - Mice MH - Neoplasm Proteins/agonists/metabolism MH - Neoplasms, Experimental/*drug therapy/metabolism/pathology MH - *Photochemotherapy MH - Receptors, Urokinase Plasminogen Activator/agonists/metabolism MH - U937 Cells MH - Urokinase-Type Plasminogen Activator/chemistry/*pharmacology MH - Xenograft Model Antitumor Assays MH - Zinc OTO - NOTNLM OT - Photosensitizer OT - Tumor-imaging OT - Tumor-targeting OT - Zinc phthalocyanine EDAT- 2014/06/28 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/06/28 06:00 PHST- 2014/03/01 00:00 [received] PHST- 2014/06/10 00:00 [revised] PHST- 2014/06/17 00:00 [accepted] PHST- 2014/06/28 06:00 [entrez] PHST- 2014/06/28 06:00 [pubmed] PHST- 2015/05/15 06:00 [medline] AID - S1742-7061(14)00282-7 [pii] AID - 10.1016/j.actbio.2014.06.026 [doi] PST - ppublish SO - Acta Biomater. 2014 Oct;10(10):4257-68. doi: 10.1016/j.actbio.2014.06.026. Epub 2014 Jun 24.