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纤维素在NaOH/尿素水溶液中作为基因载体的均相季铵化

Homogeneous quaternization of cellulose in NaOH/urea aqueous solutions as gene carriers.

作者信息

Song Yongbo, Sun Yunxia, Zhang Xianzheng, Zhou Jinping, Zhang Lina

机构信息

Department of Chemistry, Wuhan University, Wuhan 430072, China.

出版信息

Biomacromolecules. 2008 Aug;9(8):2259-64. doi: 10.1021/bm800429a. Epub 2008 Jul 19.

Abstract

Quaternized celluloses (QCs) were homogeneously synthesized by reacting cellulose with 3-chloro-2-hydroxypropyltrimethylammonium chloride (CHPTAC) in NaOH/urea aqueous solutions. The structure and solution properties of the QCs were characterized by using elemental analysis, FTIR, (13)C NMR, SEC-LLS, viscometer, and zeta-potential measurement. The results revealed that water-soluble QCs, with a degree of substitution (DS) value of 0.20-0.63, could be obtained by adjusting the molar ratio of CHPTAC to anhydroglucose unit (AGU) of cellulose and the reaction time. The QC solutions in water displayed a typical polyelectrolyte behavior, and the intrinsic viscosity ([eta]) value determined from the Fuoss-Strauss method increased with increasing DS value. Moreover, two QC samples (DS = 0.46 and 0.63) were selected and studied as gene carriers. The results of gel retardation assay suggested that QCs could condense DNA efficiently. QCs displayed relatively lower cytotoxicity as compared with PEI, and QC/DNA complexes exhibited effective transfection compared to the naked DNA in 293T cells. The quaternized cellulose derivatives prepared in NaOH/urea aqueous solutions could be considered as promising nonviral gene carriers.

摘要

通过在氢氧化钠/尿素水溶液中使纤维素与3-氯-2-羟丙基三甲基氯化铵(CHPTAC)反应,均相合成了季铵化纤维素(QC)。通过元素分析、傅里叶变换红外光谱(FTIR)、碳-13核磁共振(¹³C NMR)、尺寸排阻色谱-多角度激光光散射(SEC-LLS)、粘度计和zeta电位测量对QC的结构和溶液性质进行了表征。结果表明,通过调节CHPTAC与纤维素脱水葡萄糖单元(AGU)的摩尔比以及反应时间,可以获得取代度(DS)值为0.20-0.63的水溶性QC。QC在水中的溶液表现出典型的聚电解质行为,通过福斯-施特劳斯方法测定的特性粘度([η])值随DS值的增加而增加。此外,选择了两个QC样品(DS = 0.46和0.63)作为基因载体进行研究。凝胶阻滞试验结果表明,QC可以有效地凝聚DNA。与聚乙烯亚胺(PEI)相比,QC表现出相对较低的细胞毒性,并且与裸DNA相比,QC/DNA复合物在293T细胞中表现出有效的转染。在氢氧化钠/尿素水溶液中制备的季铵化纤维素衍生物可被认为是有前途的非病毒基因载体。

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