Zhang Tao, Yu Yuan Yuan, Li Dong, Peng Rong, Li Ying, Jiang Qing, Dai Ping, Gao Rong
College of Chemistry, Sichuan University, Chengdu, 610064, People's Republic of China.
J Mater Sci Mater Med. 2009 Mar;20(3):673-80. doi: 10.1007/s10856-008-3620-1. Epub 2008 Oct 24.
Chitosan and its derivatives are attractive non-viral vectors. To produce target-cell specificity and improve the solubility of chitosan, a novel chitosan derivative, modified with galactose and methoxy poly(ethylene glycol) (mPEG) was synthesized, and structure changes of chitosan and its derivatives were characterized. Compared to chitosan, the solution viscosity of the novel chitosan derivative drastically decreased. And, the degree of substitution (DS) of chitosan by galactose and mPEG were calculated as 0.09 and 0.30. The average diameter and zeta potential of mPEGylated galactosylated chitosan (GaC) nanoparticle containing VRMFat plasmid were 178 nm and +2.93 mV, suggesting suitable properties for gene delivery system. The gel electrophoresis confirmed that the plasmid DNA was remained completely by the mPEGylated GaC nanoparticle. And, the cytotoxic effect of mPEGylated GaC nanoparticles on human embryonic kidney (HEK 293) cells was negligible in comparison with that of control chitosans. Therefore, it is expected that the mPEGylated GaC will have the potential as a targeting gene delivery system for a further application.
壳聚糖及其衍生物是具有吸引力的非病毒载体。为了实现对靶细胞的特异性并提高壳聚糖的溶解性，合成了一种用半乳糖和甲氧基聚乙二醇（mPEG）修饰的新型壳聚糖衍生物，并对壳聚糖及其衍生物的结构变化进行了表征。与壳聚糖相比，新型壳聚糖衍生物的溶液粘度大幅降低。并且，壳聚糖被半乳糖和mPEG的取代度（DS）分别计算为0.09和0.30。含有VRMFat质粒的聚乙二醇化半乳糖化壳聚糖（GaC）纳米颗粒的平均直径和zeta电位分别为178 nm和+2.93 mV，表明其具有适合基因递送系统的性质。凝胶电泳证实聚乙二醇化GaC纳米颗粒能完全保留质粒DNA。并且，与对照壳聚糖相比，聚乙二醇化GaC纳米颗粒对人胚肾（HEK 293）细胞的细胞毒性作用可忽略不计。因此，预计聚乙二醇化GaC作为靶向基因递送系统具有进一步应用的潜力。
