Zinc phthalocyanine conjugated with the amino-terminal fragment of urokinase for tumor-targeting photodynamic therapy
Zinc phthalocyanine conjugated with the amino-terminal fragment of urokinase for tumor-targeting photodynamic therapy
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DOI：
10.1016/j.actbio.2014.06.026
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发表时间：
2014-10-01
影响因子：
9.7
通讯作者：
Huang, Mingdong
中科院分区：
文献类型：
--
作者：
Chen, Zhuo;Xu, Peng;Huang, Mingdong
由于传统化疗中多药耐药性和全身毒性发生率的增加，光动力疗法（PDT）在癌症治疗中引起了人们的广泛关注。酞菁（Pc）是PDT光敏剂的主要类别之一，具有最佳的光物理和光化学性质。当PCs靶向肿瘤特异性受体时，理想情况下可以实现更高的特异性，这也可能促进特异性药物递送。在此，我们开发了一种简单而独特的策略，通过将酞菁锌（ZnPc）通过ATF的羧基共价偶联至尿激酶型纤溶酶原激活剂（uPA）的氨基末端片段（ATE）来制备亲水性肿瘤靶向光敏剂ATF-ZnPc，uPA是负责uPA受体（uPAR，癌细胞中过度表达的生物标志物）的片段。我们证明了这种肿瘤靶向 PDT 药物在体外和体内抑制肿瘤生长的高效性。我们使用H22荷瘤小鼠的体内光学成像结果清楚地显示了ATF-ZnPc在肿瘤区域的选择性积累，从而揭示了ATF-ZnPc在除了光动力治疗之外的癌症检测和指导肿瘤切除等临床应用中的巨大潜力。 (C) 2014 Acta Materialia Inc. 由 Elsevier Ltd 出版。保留所有权利。
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 (ATE) 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. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.