Self-assembling micelle-like nanoparticles based on phospholipid-polyethyleneimine conjugates for systemic gene delivery.
Self-assembling micelle-like nanoparticles based on phospholipid-polyethyleneimine conjugates for systemic gene delivery.
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DOI：
10.1016/j.jconrel.2008.09.079
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发表时间：
2009-01-19
期刊：
影响因子：
--
通讯作者：
Torchilin VP
中科院分区：
文献类型：
--
作者：
Ko YT;Kale A;Hartner WC;Papahadjopoulos-Sternberg B;Torchilin VP
除了少数例外，在局部给药可行的情况下，基因疗法的广泛临床应用的进展需要开发有效的递送系统。在这里，我们报告了一种新的非病毒基因传递载体，“胶束样纳米粒子”（MNP）适合全身应用。MNP是通过将质粒DNA与磷脂和聚乙烯亚胺（PLPEI）的化学缀合物缩合，然后用另外含有聚乙二醇-磷脂酰乙醇胺（PEG-PE）的脂质单层包被复合物来工程化的，从而产生负载DNA的球形“硬核”纳米颗粒。MNP允许完全保护加载的DNA免于酶促降解，抵抗盐诱导的聚集，并降低细胞毒性。MNP还表现出延长的血液循环和低RES积累。静脉内注射载有编码绿色荧光蛋白（GFP）的质粒DNA的MNP导致远端肿瘤的有效转染。因此，MNP为系统性基因治疗提供了一个有前途的工具。
With few exceptions, where local administration is feasible, progress towards broad clinical application of gene therapies requires the development of effective delivery systems. Here we report a novel non-viral gene delivery vector, ‘micelle-like nanoparticle’ (MNP) suitable for systemic application. MNP were engineered by condensing plasmid DNA with a chemical conjugate of phospholipid with polyethylenimine (PLPEI) and then coating the complexes with an envelope of lipid monolayer additionally containing polyethylene glycol-phosphatidyl ethanolamine (PEG-PE), resulting in spherical ‘hard-core’ nanoparticles loaded with DNA. MNP allowed for complete protection of the loaded DNA from enzymatic degradation, resistance to salt-induced aggregation, and reduced cytotoxicity. MNP also demonstrated prolonged blood circulation and low RES accumulation. Intravenous injection of MNP loaded with plasmid DNA encoding for the Green Fluorescence Protein (GFP) resulted in an effective transfection of a distal tumor. Thus, MNP provide a promising tool for systemic gene therapy.
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