A near-infrared phthalocyanine dye-labeled agent for integrin αvβ6-targeted theranostics of pancreatic cancer
A near-infrared phthalocyanine dye-labeled agent for integrin αvβ6-targeted theranostics of pancreatic cancer
复制标题
用于整合素 α v β 6 靶向胰腺癌治疗诊断的近红外酞菁染料标记试剂
DOI：
10.1016/j.biomaterials.2015.02.093
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发表时间：
2015-06-01
期刊：
影响因子：
14
通讯作者：
Liu, Zhaofei
中科院分区：
文献类型：
--
作者：
Gao, Duo;Gao, Liquan;Liu, Zhaofei
整合素αvβ6在多种恶性肿瘤中广泛上调，但在正常器官中检测不到，这使其成为癌症诊断成像和治疗的有希望的靶点。我们利用链霉亲和素-生物素化学方法合成了一种以整合素αvβ6为靶点的近红外酞菁染料标记剂Dye-SA-B-HK，并研究了其是否可用于胰腺癌小鼠模型的肿瘤成像、光学成像引导手术和光疗。染料-SA-B-HK在体内外与整合素αvβ6特异性结合，具有较高的受体结合亲和力。利用小动物光学成像技术，对BxPC-3人胰腺癌皮下移植瘤和原位移植瘤进行了体内检测。在光学图像引导下，原位生长的胰腺癌病变可以通过手术成功切除。在光照条件下，Dye-SA-B-HK在体内外均表现出显著的抗肿瘤作用。F-18-FDG正电子发射断层扫描(PET)成像和体外荧光染色证实了Dye-DA-B-HK光疗后肿瘤细胞增殖的减少。组织芯片结果显示，整合素αvβ6在超过95%的人胰腺癌组织中过表达，表明Dye-DA-B-HK的治疗应用具有明显的翻译潜力。总体而言，这项研究的结果表明，整合素αvβ6特异性染料SA-B-HK是治疗胰腺癌的一种有前途的治疗药物。(C)2015爱思唯尔有限公司。保留所有权利。
Integrin alpha v beta 6 is widely upregulated in variant malignant cancers but is undetectable in normal organs, making it a promising target for cancer diagnostic imaging and therapy. Using streptavidin-biotin chemistry, we synthesized an integrin alpha v beta 6-targeted near-infrared phthalocyanine dye-labeled agent, termed Dye-SA-B-HK, and investigated whether it could be used for cancer imaging, optical imaging-guided surgery, and phototherapy in pancreatic cancer mouse models. Dye-SA-B-HK specifically bound to integrin alpha v beta 6 in vitro and in vivo with high receptor binding affinity. Using small-animal optical imaging, we detected subcutaneous and orthotopic BxPC-3 human pancreatic cancer xenografts in vivo. Upon optical image-guidance, the orthotopically growing pancreatic cancer lesions could be successfully removed by surgery. Using light irradiation, Dye-SA-B-HK manifested remarkable antitumor effects both in vitro and in vivo. F-18-FDG positron emission tomography (PET) imaging and ex vivo fluorescence staining validated the observed decrease in proliferation of treated tumors by Dye-DA-B-HK phototherapy. Tissue microarray results revealed overexpression of integrin alpha v beta 6 in over 95% cases of human pancreatic cancer, indicating that theranostic application of Dye-DA-B-HK has clear translational potential. Overall, the results of this study demonstrated that integrin alpha v beta 6-specific Dye-SA-B-HK is a promising theranostic agent for the management of pancreatic cancer. (C) 2015 Elsevier Ltd. All rights reserved.