Stabilizing of plasmid DNA in vivo by PEG-modified cationic gold nanoparticles and the gene expression assisted with electrical pulses
Stabilizing of plasmid DNA in vivo by PEG-modified cationic gold nanoparticles and the gene expression assisted with electrical pulses
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DOI：
10.1016/j.jconrel.2005.12.022
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发表时间：
2006-04-10
影响因子：
10.8
通讯作者：
Niidome, T
中科院分区：
文献类型：
--
作者：
Kawano, T;Yamagata, M;Niidome, T
本研究旨在探讨将聚乙二醇修饰的阳离子金纳米颗粒与电穿孔相结合用于体内基因递送的益处。在2-氨基乙硫醇和mPEG-SH存在下，采用NaBH4还原HAuCl4制备了peg修饰的阳离子金纳米颗粒。粒子的ζ电位接近中性（+0.1 mV）。在与质粒DNA形成w/w比为8.4的复合物后，纳米颗粒复合物长度为90 nm，持续时间至少为60分钟，并表现出负的ζ电位。静脉注射DNA-纳米颗粒复合物后，注射后120分钟血液中检测到20%的金，注射后5分钟血液中检测到5%的DNA，表明peg修饰的纳米颗粒在血液中稳定循环，但与颗粒结合的DNA在循环过程中降解。在注射dna纳米颗粒复合物后，将电穿孔应用于肝脏叶，在脉冲叶中特别观察到显著的基因表达。我们得出结论，peg修饰的纳米颗粒在血液流动中比在裸DNA的情况下更稳定地维持DNA，电穿孔有助于限制肝脏有限区域循环DNA的基因表达。(c) 2006 Elsevier B.V.版权所有
This study aimed to investigate the benefits of combining the use of PEG-modified cationic gold nanoparticles with electroporation for in vivo gene delivery. PEG-modified cationic gold nanoparticles were prepared by NaBH4 reduction of HAuCl4 in the presence of 2-aminoethanethiol and mPEG-SH. Zeta-potential of the particles was nearly neutral (+0.1 mV). After forming complexes with plasmid DNA at a w/w ratio of 8.4, nanoparticle complexes were 90 nm for at least 60 min and showed a negative zeta-potential. After intravenous injection of DNA-nanoparticle complexes, 20% of gold were detected in blood at 120 min after injection and 5% of DNA were observed in blood after 5 min, suggesting that PEG-modified nanoparticles were stably circulating in the blood flow, but some of the DNA bound to particles degraded during circulation. When electroporation was applied to a lobe of the liver following injection of DNA-nanoparticle complexes, significant gene expression was specifically observed in the pulsed lobe. We concluded that PEG-modified nanoparticles maintained DNA more stably in the blood flow than in the case of naked DNA and electroporation assisted in restricted gene expression of circulating DNA in limited areas of the liver. (c) 2006 Elsevier B.V. All rights reserved.