温度和pH敏感高分子含钆核磁共振成像造影剂的合成及性能

doi:10.7503/cjcu20150663

高等学校化学学报 ›› 2016, Vol. 37 ›› Issue (1): 155.doi: 10.7503/cjcu20150663

温度和pH敏感高分子含钆核磁共振成像造影剂的合成及性能

刘瑞清¹, 梁爽², 江存¹, 徐祖顺¹(), 徐海波²

1. 湖北大学有机化工新材料湖北省协同创新中心, 武汉 430062
2. 华中科技大学同济医学院协和医院放射科, 武汉 430030

收稿日期:2015-08-20 出版日期:2016-01-10 发布日期:2015-12-20
基金资助:
国家自然科学基金(批准号: 51273058, 81171386, 81372369)资助

Synthesis and Proporties of Temperature and pH-sensitive and Gadolinium Contained Polymeric Magnetic Resonance Imaging Contrast Agent^†

LIU Ruiqing¹, LIANG Shuang², JIANG Cun¹, XU Zushun^1,^*(), XU Haibo^2,^*

1. Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials; Ministry of Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei University, Wuhan 430062, China
2. Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Received:2015-08-20 Online:2016-01-10 Published:2015-12-20
Contact: XU Zushun,XU Haibo E-mail:xuhaibo1120@hotmail.com
Supported by:
† Supported by the National Natural Science Foundation of China(Nos.51273058, 81171386, 81372369)

摘要/Abstract

摘要：

以N-异丙基丙烯酰胺为温度敏感单体, 以甲基丙烯酸为pH敏感单体, 与三丙烯酸菲洛啉钆进行无皂乳液聚合, 一步合成了具有温度和pH敏感的高分子含钆核磁共振成像(MRI)造影剂(TPRPP). 动态光散射测试结果表明, TPRPP的粒径随温度或pH值的变化而发生较大的改变. 体外MRI测试结果表明, TPRPP的横向弛豫时间(T₁)的加权弛豫率约为11.3 L/(mmol·s), 为临床造影剂Magnevist^?的2.6倍. 体内MRI结果表明, TPRPP在肝和脾中具有明显的正增强效果. 研究结果表明, TPRPP是一种优异的多功能MRI造影剂, 具有极大的临床研究价值.

关键词: 温度和pH敏感高分子, 核磁共振成像, 无皂乳液聚合, 钆造影剂

Abstract:

Paramagnetic, temperature and pH-sensitive polymeric particles were prepared with N-isopropylacrylamide, methacrylic acid, styrene, and polymerizable Gd(AA)₃phen·H₂O using emulsifier-free emulsion polymerization technique. Dynamic light scattering result shows that the diameter of the polymeric particles changes by about 60 nm as a result of variations in either the temperature or pH, indicating that the particles are pH and temperature-sensitive. The T₁-weighted relaxivity values at 3 T are about 11.3 L/(mmol·s) which is 2.6 times higher than clinical Magnevist^?. In vivo MR imaging reveals that the TPRPPs can be effectively imaged in the liver and spleen, suggesting that they are excellent magnetic resonance imaging agents.

Key words: Temperature and pH-sensitive polymer, Magnetic resonance imaging(MRI), Emulsifier-free emulsion polymerization, Gadolinium contrast agent

中图分类号:

O633

TrendMD:

刘瑞清, 梁爽, 江存, 徐祖顺, 徐海波. 温度和pH敏感高分子含钆核磁共振成像造影剂的合成及性能. 高等学校化学学报, 2016, 37(1): 155.

LIU Ruiqing, LIANG Shuang, JIANG Cun, XU Zushun, XU Haibo. Synthesis and Proporties of Temperature and pH-sensitive and Gadolinium Contained Polymeric Magnetic Resonance Imaging Contrast Agent^†. Chem. J. Chinese Universities, 2016, 37(1): 155.

图/表 7

Scheme 1 Synthetic routes of TPRPP

Fig.1 FTIR spectra of Gd(AA)3phen·H2O(a), TPRPP1(b) and TPRPP(c)

Fig.2 TEM images of TPRPP1(A) and TPRPP(B)

Fig.3 Dh of TPRPP as function of temperature(A), pH(B), variation in Dh of TPRPP as alternate temperature of 25 and 37 ℃(C) and alternate pH value of 2.0 and 7.4(D)^ The pH of (A) and (C) is 6.0; the temperature of (B) and (D) is 25 ℃.

Fig.4 Cell viability against Hela cells assessed by standard MTT assay

Fig.5 T1-weighted relaxivity of TPRPP^The longitudinal relaxation time(T1) is measured on a clinical 3.0 T MR scanner at various Gd(Ⅲ) concentrations.

Fig.6 T1-weighted MR images taken at different time points^T1/min: (A) 0; (B) 15; (C) 30; (D) 60; (E) 120; (F) 360.

参考文献 24

[1]	Li Y., Beija M., Laurent S., Elst L. V., Muller R. N., Duong H. T. T., Lowe A. B., Davis T. P., Boyer C., Macromolecules,2012, 45(10), 4196—4204
[2]	Liu Y. J., Feng L. X., Liu T. X., Zhang L., Yao Y., Yu D. X., Wang L. L., Zhang N., Nanoscale,2014, 6(6), 3231—3242
[3]	Cheng Z., Thorek D. L., Tsourkas A., Angew. Chem. Int. Ed. Engl., 2010, 49(2), 346—350
[4]	Liu Y. G., Zhang N., Biomaterials,2012, 33(21), 5363—5375
[5]	Wu X., Wang Z., Zhu D., Zong S., Yang L., Zhong Y., Cui Y., ACS Appl. Mater. Interfaces, 2013, 5(21), 10895—10903
[6]	Davies G. L., Kramberger I., Davis J. J., Chem. Commun.(Camb), 2013, 49(84), 9704—9721
[7]	Nwe K., Huang C. H., Tsourkas A., J. Med. Chem., 2013, 56(20), 7862—7869
[8]	Kim K. S., Park W., Hu J., Bae Y. H., Na K., Biomaterials,2014, 35(1), 337—343
[9]	Kono K., Nakashima S., Kokuryo D., Aoki I., Shimomoto H., Aoshima S., Maruyama K., Yuba E., Kojima C., Harada A., Ishizaka Y., Biomaterials,2011, 32(5), 1387—1395
[10]	Liu Q. M., Zhu H. Z., Qin J. Y., Dong H. Q., Du J. Z., Biomacromolecules,2014, 15(5), 1586—1592
[11]	Liu Q. M., Chen S., Chen J., Du J. Z., Macromolecules,2015, 48(3), 739—749
[12]	Shuhendler A. J., Staruch R., Oakden W., Gordijo C. R., Rauth A. M., Stanisz G. J., Chopra R., Wu X. Y., J. Control. Release, 2012, 157(3), 478—484
[13]	Shalviri A., Foltz W. D., Cai P., Rauth A. M., Wu X. Y., J. Control. Release, 2013, 167(1), 11—20
[14]	Li X., Qian Y., Liu T., Hu X., Zhang G., You Y., Liu S., Biomaterials,2011, 32(27), 6595—6605
[15]	Xu Z. S., Liu R. Q., Liang S., Jiang C., Wang X., The Synthesis and Application of a Polymerizable Gadolinium Complex, CN 104672258A,2015-06-03
	(徐祖顺, 刘瑞清, 梁爽, 江存, 汪鑫. 一种含双键水溶性钆配合物及其合成方法和应用, CN 104672258A, 2015-06-03)
[16]	Peng J., Qi T., Liao J., Fan M., Luo F., Li H., Qian Z., Nanoscale,2012, 4(8), 2694—2704
[17]	Zhu H. E., Tao J., Wang W. H., Zhou Y. J., Li P. H., Li Z., Yan K., Wu S. L., Yeung K. W., Xu Z. S., Xu H. B., Chu P. K., Biomaterials,2013, 34(9), 2296—2306
[18]	Ding X., Sun Z., Zhang W., Peng Y., Chan A. S. C., Li P., Colloid. Polym. Sci., 2000, 278, 459—463
[19]	Niu S. Y., Jin J., Jin X. L., Yang Z. Z., Solid State Sciences, 2000, 4, 1103—1106
[20]	Chan A., Orme R. P., Fricker R. A., Roach P., Adv. Drug. Deliv. Rev., 2013, 65(4), 497—514
[21]	Kharlampieva E., Sukhishvil S. A., Macromolecules,2003, 36, 9950—9956
[22]	Rahane S. B., Floyd J. A., Metters A. T., Kilbey S. M., Adv. Funct. Mater., 2008, 18(8), 1232—1240
[23]	Villaraza A. J., Bumb A., Brechbiel M. W., Chem. Rev., 2010, 110(5), 2921—2959
[24]	Shen C., New E. J., Curr. Opin. Chem. Biol., 2013, 17(2), 158—166

温度和pH敏感高分子含钆核磁共振成像造影剂的合成及性能

Synthesis and Proporties of Temperature and pH-sensitive and Gadolinium Contained Polymeric Magnetic Resonance Imaging Contrast Agent^†

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温度和pH敏感高分子含钆核磁共振成像造影剂的合成及性能

Synthesis and Proporties of Temperature and pH-sensitive and Gadolinium Contained Polymeric Magnetic Resonance Imaging Contrast Agent†

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Synthesis and Proporties of Temperature and pH-sensitive and Gadolinium Contained Polymeric Magnetic Resonance Imaging Contrast Agent^†