Glycosaminoglycan-resistant and pH-sensitive lipid-coated DNA complexes produced by detergent removal method
Glycosaminoglycan-resistant and pH-sensitive lipid-coated DNA complexes produced by detergent removal method
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DOI：
10.1016/j.jconrel.2008.07.018
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发表时间：
2008-10-21
影响因子：
10.8
通讯作者：
Urtti, Arto
中科院分区：
文献类型：
--
作者：
Lehtinen, Julia;Hyvonen, Zanna;Urtti, Arto
阳离子聚合物在体外条件下是有效的基因传递载体，但由于与胞外多阴离子，即糖胺多聚糖(GAG)的相互作用，这些载体在体内可能失败。本研究的目的是开发一种稳定的基因递送载体，该载体可以在酸性内体pH下被激活。以1，2-二油基磷脂酰乙醇胺(DOPE)和琥珀酸甘油酯(CHEMS)(3：2)为包覆剂，采用去污剂和乙醇注射法制备脂质体两种包覆方法对阳离子DNA/PEI复合体进行包覆。只有去掉洗涤剂才能产生稳定的抗GAGS的脂膜DNA复合体，但在低pH值下对模拟脂质体的内体具有膜活性。由于包衣复合体的细胞摄取率较低，它们的转染率相对较高。包衣复合物的聚乙二醇化增加了它们的细胞摄取，但降低了对pH的敏感性。因此，去污剂是生产稳定的、但可酸激活的、包被脂类的DNA复合体的一种更好的方法。(C)2008爱思唯尔B.V.保留所有权利。
Cationic polymers are efficient gene delivery vectors in in vitro conditions, but these carriers can fail in vivo due to interactions with extracellular polyanions, i.e. glycosaminoglycans (GAG). The aim of this study was to develop a stable gene delivery vector that is activated at the acidic endosomal pH. Cationic DNA/PEI complexes were coated by 1,2-dioleylphosphatidylethanolamine (DOPE) and cholesteryl hemisuccinate (CHEMS) (3:2 mol/mol) using two coating methods: detergent removal and mixing with liposomes prepared by ethanol injection. Only detergent removal produced lipid-coated DNA complexes that were stable against GAGs, but were membrane active at low pH towards endosome mimicking liposomes. In relation to the low cellular uptake of the coated complexes, their transfection efficacy was relatively high. PEGylation of the coated complexes increased their cellular uptake but reduced the pH-sensitivity. Detergent removal was thus a superior method for the production of stable, but acid activatable, lipid-coated DNA complexes. (C) 2008 Elsevier B.V. All rights reserved.