靶向肿瘤血管诱发血栓栓塞体系的建立及活性鉴定

王显江,王池真,陈小丽,李哲,罗伶俐,吕莎,梅理祥,周娇,王生育,颜江华*

中国药学杂志 ›› 2014, Vol. 49 ›› Issue (17) : 1508-1512.

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中国药学杂志 ›› 2014, Vol. 49 ›› Issue (17) : 1508-1512. DOI: 10.11669/cpj.2014.17.008
论 著

靶向肿瘤血管诱发血栓栓塞体系的建立及活性鉴定

  • 王显江1,王池真1,陈小丽1,李哲1,罗伶俐2,吕莎1,梅理祥1,周娇1,王生育1,颜江华1*
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Establishment and Characterization of a Targeting Tumor Vesseles System for Inducing Thrombosis

  • WANG Xian-jiang1, WANG Chi-zhen 1, CHEN Xiao-li 1, LI Zhe1, LUO Ling-li2, L Sha1, MEI Li-xiang1, ZHOU Jiao1, WANG Sheng-yu1, YAN Jiang-hua1*
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摘要

目的 建立一种新型的靶向高效诱发肿瘤血管血栓栓塞体系磁流体-神经纤维网蛋白1抗体A6-链霉亲和素:生物素-短截型组织因子(MF-A6-SA:B-tTF)。方法 化学交联技术制备神经纤维网蛋白1抗体A6-链霉亲和素、磁流体-神经纤维网蛋白1抗体A6-链霉亲和素和生物素-短截型组织因子交联物,凝血因子X活化实验鉴定复合体系活化凝血因子X的活力,荧光显微镜技术和普鲁士蓝染色法同时观察施加外界磁场后复合体系的靶向作用,凝血实验直接观察复合体系引入链霉亲和素:生物素的生物放大效应,体内生物分布实验观察复合体系的安全性。结果 成功制备磁流体-神经纤维网蛋白1抗体A6-链霉亲和素及生物素-短截型组织因子,磁流体-神经纤维网蛋白1抗体A6-链霉亲和素:生物素-短截型组织因子体系保留有高效激活凝血因子X的活性,与靶点的结合具有靶向性及高效富集性,体内实验证实能安全有效诱发肿瘤血管栓塞。结论 成功制备的具有靶向诱发肿瘤血管血栓栓塞体系磁流体-神经纤维网蛋白1抗体A6-链霉亲和素:生物素-短截型组织因子为进一步探索肿瘤血管的靶向治疗奠定基础。

Abstract

OBJECTIVE To establish a novel targeting tumor vessels system MF-A6-SA:B-tTF for efficiently inducing thrombosis. METHODS Chemical cross-linking technique was used to prepare a cross-linking agent of the A6-Streptavidin (A6-SA), MF-A6-SA and Biotein-tTF (B-tTF). FX coagulation assay was used to test MF-A6-SA:B-tTF system′s FX activity. Fluorescence microscopy and prussian blue staining were used to simultaneously observe the targeting activity of MF-A6-SA:B-tTF with an external magnetic field. Hemagglutination was directly used to study the system′s biological amplification by SA/B. Biodistribution experiment was used to observe the toxicity of MF-A6-SA:B-tTF. RESUTLS MF-A6-SA and B-tTF were successfully prepared. MF-A6-SA:B-tTF system could activate FX, inducing the blood coagulating cascade powerfully. MF-A6-SA:B-tTF could be accumulated to the desired target area with targeting and induce thrombosis in tumor blood vessels in vitro and in vivo. CONCLUSION The double targeting tumor vessels system MF-A6-SA:B-tTF maybe provide a basis for developing the tumor blood vessels targeting therapy.

关键词

靶向 / 神经纤维网蛋白1单克隆抗体 / 短截型组织因子 / 磁流体 / 血管栓塞 / 抗肿瘤

Key words

targeting / anti-neuropilin 1 (NRP1) antibody / truncated tissue factor(tTF) / magnetic fluid / thrombosis / anti-tumor

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王显江,王池真,陈小丽,李哲,罗伶俐,吕莎,梅理祥,周娇,王生育,颜江华*. 靶向肿瘤血管诱发血栓栓塞体系的建立及活性鉴定[J]. 中国药学杂志, 2014, 49(17): 1508-1512 https://doi.org/10.11669/cpj.2014.17.008
WANG Xian-jiang, WANG Chi-zhen , CHEN Xiao-li , LI Zhe, LUO Ling-li, L Sha, MEI Li-xiang, ZHOU Jiao, WANG Sheng-yu, YAN Jiang-hua*. Establishment and Characterization of a Targeting Tumor Vesseles System for Inducing Thrombosis[J]. Chinese Pharmaceutical Journal, 2014, 49(17): 1508-1512 https://doi.org/10.11669/cpj.2014.17.008
中图分类号: R965   

参考文献

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基金

国家自然科学基金资助项目(30973485,81172970);国家级大学生创新性实验项目(201210384134)
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