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: Zhuo Chen, Peng Xu, Jincan Chen, Hongwei Chen, Ping Hu, Xueyuan Chen, Lin Lin, Yunmei Huang, Ke Zheng, Shanyong Zhou, Rui Li, Song Chen, Jianyong Liu, Jinping Xue, Mingdong Huang
• Journal: Acta biomaterialia (Acta Biomater) Vol. 10 Issue 10 Pg. 4257-68 (Oct 2014) ISSN: 1878-7568 [Electronic] England
• PMID: 24969665 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Indoles
• Isoindoles
• Neoplasm Proteins
• Receptors, Urokinase Plasminogen Activator
• Urokinase-Type Plasminogen Activator
• Zinc
• phthalocyanine

Topics

• Animals
• Biomarkers, Tumor (agonists, metabolism)
• Drug Delivery Systems (methods)
• Humans
• Indoles (chemistry, pharmacology)
• Isoindoles
• Mice
• Neoplasm Proteins (agonists, metabolism)
• Neoplasms, Experimental (drug therapy, metabolism, pathology)
• Photochemotherapy
• Receptors, Urokinase Plasminogen Activator (agonists, metabolism)
• U937 Cells
• Urokinase-Type Plasminogen Activator (chemistry, pharmacology)
• Xenograft Model Antitumor Assays
• Zinc