Synthesis and Characterization of the Hexachlorotriphosphaxene Cross-linked Oligo(ethyleneimine) as Gene Carrier

Abstract

Abstract: Hyperbranched oligo(ethyleneimine) with molecular weight of 600 was carried out reaction with hexachlorotriphosphazene in anhydrous chloroform to synthesize a degradable and cross-linked polymer as a non-viral gene carrier. The 1H NMR spectra confirmed the formation of the polymer and its average molecular weight was obtained by GPC with HAc/NaAc buffering solution of pH=4.4 as fluent phase. The polymer compressed DNA into stable complexes in diameter of about 150 nm and zeta potential of 30—40 mV measured by dynamic light scattering. Besides, when the mass ratio of polymer and DNA was 0.4, the plasmids were fully retarded in 1% agarose gel by gel retardation electrophoresis. The cytotoxicity and transfection efficiency were characterized by HeLa cells in vitro. It was indicated that the best transfection efficiency of polymer with lower cytotoxicity was three times higher than that of PEI-25K. Therefore, the synthesized polymer may have good potential applications as non-viral gene carriers.

Key words: Hexachlorotriphosphazene, Oligo(ethyleneimine), Gene carrier, Transfection, Cytotoxicity

TrendMD:

LI Fei-Fan, TIAN Hua-Fu, CHEN Lei, XIA Jia-Liang, CHEN Xue-Si*, JING Xia-Bin. Synthesis and Characterization of the Hexachlorotriphosphaxene Cross-linked Oligo(ethyleneimine) as Gene Carrier[J]. Chem. J. Chinese Universities, 2010, 31(9): 1896.

References

[1]Green J. J., Langer R., Anderson D. G.. Accounts Chem. Res.[J], 2008, 41(6): 749—759 [2]Wong S. Y., Pelet J. M., Putnam D.. Prog. Polym. Sci.[J], 2007, 32(8/9): 799—837 [3]Morille M., Passirani C., Vonarbourg A., Clavreul A., Benoit J. P.. Biomaterials[J], 2008, 29(24/25): 3477—3496 [4]Boussif O., Lezoualch F., Zanta M. A., Mergny M. D., Scherman D., Demeneix B., Behr J. P.. P.N.A.S.[J], 1995, 92(16): 7297—7301 [5]Lungwitz U., Breunig M., Blunk T., Goepferich A.. Eur. J. Pharm. Biopharm.[J], 2005, 60(2): 247—266 [6]Tian H. Y., Xiong W., Wei J. Z., Wang Y., Chen X. S., Jing X. B., Zhu Q. Y.. Biomaterials[J], 2007, 28(18): 2899—2907 [7]TIAN Hua-Yu(田华雨), XIA Jia-Liang(夏加亮), LIN Hao(林浩), CHEN Lei(陈磊), CHEN Xue-Si(陈学思), LI Yue-Sheng(李悦生), JING Xia-Bin(景遐斌). Chem. J. Chinese Universities(高等学校化学学报)[J], 2006, 27(9): 1771—1774 [8]FU Hui-Li(付慧莉), CHENG Si-Xue(程巳雪), ZHUO Ren-Xi(卓仁禧). Acta Polym. Sin.(高分子学报)[J], 2009, (2): 97—103 [9]Forrest M. L., Koerber J. T., Pack D. W.. Bioconjugate Chem.[J], 2003, 14(5): 934—940 [10]Ahn C. H., Chae S. Y., Bae Y. H., Kim S. W.. J. Control. Release[J], 2002, 80(1—3): 273—282 [11]Jere D., Xu C. X., Arote R., Yun C. H., Cho M. H., Cho C. S.. Biomaterials[J], 2008, 29(16): 2535—2547 [12]Allcock H. A., Kugel R. L.. J. Am. Chem. Soc.[J], 1965, 87(18): 4216—4217 [13]Andrianov A. K.. J. Inorg. Organomet. P.[J], 2006, 16(4): 397—406 [14]Allcock H. R., Kwon S.. Macromolecules[J], 1989, 22(1): 75—79 [15]Allcock H. R., Austin P. E., Neenan T. X., Sisko J. T., Blonsky P. M., Shriver D. F.. Macromolecules[J], 1986, 19(6): 1508—1512 [16]Luten J., van Steenis J. H., van Someren R., Kemmink J., Schuurmans-Nieuwnbroek N. M. E., Koning G. A., Crommelin D. J. A., Van Nostrum C. F., Hennink W. E.. J. Control. Release[J], 2003, 89(3): 483—497 [17]Luten J., van Steenbergen M. J., Lok M. C., de Graaff A. M., van Nostrum C. F., Talsma H., Hennink W. E.. Eur. J. Pharm. Sci.[J], 2008, 33(3): 241—251 [18]Jiang X. L., van der Horst A., van Steenbergen M. J., Akeroyd N., van Nostrum C. F., Schoenmakers P. J., Hennink W. E.. Pharm. Res.[J], 2006, 23(3): 595—603 [19]Petersen H., Fechner P. M., Fischer D., Kissel T.. Macromolecules[J], 2002, 35(18): 6867—6874 [20]CHEN Lei(陈磊), TIAN Hua-Yu(田华雨), CHEN Xue-Si(陈学思), PARK Taegwan(朴泰宽), MARUYAMA Atsushi(丸山厚), JING Xia-Bin(景遐斌). Acta Polym. Sin.(高分子学报)[J], (6): 499—505 [21]YUAN Ren-Xu(苑仁旭), ZUO Yu-Fang(左瑜芳), XIAO Zhong-Peng(肖中鹏), HUANG Wen-Lin(黄文林), SHUAI Xin-Tao(帅心涛). Acta Polym. Sin.(高分子学报)[J], 2009, (2): 104—110 [22]LI Lai-Sheng(李来胜), TONG Jing(童景), WU Juan(吴卷), DU Jin-Zhi(杜金志), WANG Jun(王均). Acta Polym. Sin.(高分子学报)[J], 2009, (3): 257—263