Synthetic of PGMA-EDA-g-PEG-g-DS@IO as a Magnetic Resonance Contrast Agent for Atherosclerosis†

doi:10.7503/cjcu20150391

Abstract

Abstract:

To design a new magnetic resonance(MR) imaging contrast agent of atherosclerosis, poly(glycidyl methacrylate)-graft-ethane diamine(PGMA-g-EDA) was prepared by the ring-opening reaction of PGMA which was synthesized by atom transfer radical polymerization(ATRP). Poly-ethylene glycol(PEG) and dextran sulfate(DS) were graft modified to PGMA-g-EDA continuously via amidation reaction and reductive amination to synthesis PGMA-EDA-g-PEG-g-DS. The structure and properties of PGMA-EDA-g-PEG-g-DS were characterized through nuclear magnetic resonance(¹H NMR). Fourier transform infrared spectroscopy(FTIR) and gel permeation chromatography(GPC). The superparamagnetic iron oxide nanoparticles(IONPs) were coated with PGMA-EDA-g-PEG-g-DS by ligand exchange to prepare water-soluble IO. The transmission electron microscopy(TEM) analysis indicated that micelles were well dispersed in water and had uniform sizes. The result of thermogravimetric analysis(TGA) indicated that about 70%(mass fraction) polymers coated on the surface of IO. The cell counting kit(CCK) assay showed no significant toxicity to RAW264.7. The above results confirm that PGMA-EDA-g-PEG-g-DS@IO can be used as a potential contrast agent for atherosclerosis MR imaging.

Key words: Contrast agent of atherosclerosis, Magnetic resonance imaging, Iron oxide nanoparticles, Dextran sulfate, Ethane diamine, Polyethylene glycol, Poly(glycidyl methacrylate)

CLC Number:

O631

TrendMD:

HU Qi, FANG Chao, ZHAO Wai’ou, LI Yapeng, CHEN Xia, WANG Jingyuan. Synthetic of PGMA-EDA-g-PEG-g-DS@IO as a Magnetic Resonance Contrast Agent for Atherosclerosis^†[J]. Chem. J. Chinese Universities, 2015, 36(10): 2061.

Figures/Tables 8

Scheme 1 Synthesis of PGMA-EDA-g-PEG-g-DS copolymer and PGMA-EDA-g-PEG-g-DS@IO

Fig.1 1H NMR spectra of PGMA(A), PGMA-EDA-g-PEG(B) and PGMA-EDA-g-PEG-g-DS(C)^Peak numbers are corresponding to the stations for compounds in Scheme 1.

Fig.2 FTIR spectra of PGMA(a), PGMA-EDA-g-PEG(a) and PGMA-EDA-g-PEG-g-DS(c)

Fig.3 GPC curves of PGMA(a), PGMA-EDA-g-PEG(b) and PGMA-EDA-g-PEG-g-DS(c)

Fig.4 TEM images of initial IONPs(A) and PGMA-EDA-g-PEG-g-DS@IO(B)

Fig.5 DLS spectra of initial IONPs(A) in chloroform and PGMA-EDA-g-PEG-g-DS@IO(B) in water

Fig.6 TGA curve of PGMA-EDA-g-PEG-g-DS@IO at 10 ℃/min

Fig.7 VSM analysis of PGMA-EDA-g-PEG-g-DS@IO

References 24

[1]	Park K., Hong H. Y., Moon H. J., Lee B. H., Kim I. S., Kwon I. C., Rhee K., J. Controlled Release, 2008, 128, 217—223
[2]	Libby P., Nature, 2002, 420(6917), 868—874
[3]	Falk E., Journal of the American College of Cardiology, 2006, 47(8), C7—C12
[4]	Zhou J. L., Wan F. X., Yu K. C.,Ding S. W., Chem. J. Chinese Universities, 2005, 26(8), 1391—1394
	(周锦兰, 万福贤, 俞开潮, 丁尚武. 高等学校化学学报,2005, 26(8), 1391—1394)
[5]	Barkhausen J., Ebert W., Heyer C., Debatin J. F., Weinmann H. J., Circulation, 2003, 108(5), 605—609
[6]	Ruehm S. G., Corot C., Vogt P., Kolb S., Debatin J. F., Circulation, 2001, 103, 415—422
[7]	Winter P. M., Morawski A. M., Caruthers S. D., Fuhrhop R. W., Zhang H. Y., Williams T. A., Allen J. S., Lacy E. K., Robertson J. D., Lanza G. M., Wickline S. A., Circulation, 2003, 108, 2270—2274
[8]	Liu H., Design and Synthesis of Targeted Nanoprobes Based on Dendrimer PAMAM, Jilin University,Changchun, 2015
	(刘环. 以树枝状分子PAMAM为载体的靶向纳米探针的设计与合成, 长春: 吉林大学, 2015)
[9]	Peters D., Kastantin M., Kotamraju V. R., Karmali P. P., Gujraty K., Tirrell M., Ruoslahti E., Proc. Natl. Acad. Sci. U. S. A., 2009, 106, 9815—9819
[10]	Dong G. Y., Gurusamy S., Soyoung S., Carbohydrate Polymers, 2014, 101, 1225—1233
[11]	Andrew N., Lowell Qiao H., Liu T., Bioconjugate Chem., 2012, 23, 2313—2319
[12]	Xu L., Li Y. Y., Sun H. Y., Drug Discovery Today, 2013, 18, 11—12
[13]	Zhang N., Kevin P. F., Arun P., Daniel A., Nature Medicine, 2013, 19, 4
[14]	You D. G., Saravanakumar G., Son S., Han H. S., Carbohydrate Polymers, 2014, 101, 1225—1233
[15]	Di M. M., Sadun C., Port M., Guilbert I., Couvreur P., Dubernet C., InternationalJournal of Nanomedicine, 2007, 2(4), 609—622
[16]	Hernandez O. S., Soliman G. M., Winnik F. M., Polymer, 2007, 48, 921—930
[17]	Houga C., Giermanska J., Lecommandoux S., Biomacromolecules, 2009, 10, 32—40
[18]	Chauvierre C., Labarre D., Couvreur P., Vauthier C., Macromolecules, 2003, 36, 6018—6027
[19]	Wang J. S., Matyjaszewski K., J. Am. Chem. Soc, 1995, 117, 5614—5615
[20]	Sa Z. P., Liu Y. J., Zhu M., Li Y. X., Wang J. Y., Chem. J. Chinese Universities, 2013, 34(7), 1770—1775
	(撒宗朋, 刘彦晶, 李亚鹏, 祝明, 李玉祥. 高等学校化学学报,2013, 34(7), 1770—1775)
[21]	Moormann A. E., Synthetic Communications, 1993, 23(6), 789—795
[22]	Wang Y.Z., Zhu M., Huang H. L., Li Y. X., Li Y. P., Wang J. Y.,Acta Polymerica Sinica, 2013, (8), 1039—1046
	(王玉珍, 祝明, 黄海龙, 李玉祥, 李亚鹏, 王静媛. 高分子学报, 2013, (8), 1039—1046)
[23]	Schatz C., Louguet S., Le M., Lecommandoux S., Angewandte Chemie International Edition, 2009, 48(14), 2572—2575
[24]	Yang L., Zhang L. M., Carbohydrate Polymers, 2009, 76(3), 349—361