Cationic silica nanoparticles as gene carriers:: Synthesis, characterization and transfection efficiency in vitro and in vivo

Cationic silica nanoparticles as gene carriers:: Synthesis, characterization and transfection efficiency in vitro and in vivo
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DOI:
10.1166/jnn.2004.120
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发表时间:
2004-09-01
影响因子:
--
通讯作者:
Lehr, CM
Lehr, CM
中科院分区:
工程技术4区
文献类型:
--
作者:
Kumar, MNVR;Sameti, M;Lehr, CM

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本研究研究了阳离子SiO2纳米颗粒用于体内基因转移的潜力。采用氨基-己基-氨基-丙基三甲氧基硅烷(AHAPS)制备了表面改性的阳离子SiO2纳米粒子。在pH = 7.4下纳米颗粒的ζ电位从-31.4mV(未改性的颗粒; IOnm)变化至+9.6mV(通过AHAPS改性)。在80(w/w纳米颗粒/DNA比率)的颗粒比率下实现DNA在纳米颗粒表面的完全固定。表面修饰的纳米颗粒尺寸为42 nm,分布范围为10-100 nm。在Cos-1细胞中测试这些颗粒对pCMV β报告基因的抑制能力,并且在FCS和氯喹以80的颗粒比存在下获得最佳结果。这些纳米颗粒被测试其在小鼠肺中体内转移基因的能力,并且与单独的EGFP相比,发现二氧化硅颗粒的表达水平增加了两倍。观察到非常低或没有细胞毒性,表明二氧化硅纳米颗粒作为基因转染的潜在替代物。
The potential of cationic SiO2 nanoparticles was investigated for in vivo gene transfer in this study. Cationic SiO2 nanoparticles with surface modification were generated using amino-hexyl-amino-propyltri-methoxysilane (AHAPS). The zeta potential of the nanoparticles at pH = 7.4 varied from -31.4 mV (unmodified particles; 10 nm) to +9.6 mV (modified by AHAPS). Complete immobilization of DNA at the nanoparticle surface was achieved at a particle ratio of 80 (w/w nanoparticle/DNA ratio). The surface modified nanoparticle had a size of 42 nm with a distribution from 10-100 nm. The ability of these particles to transfect pCMVbeta reporter gene was tested in Cos-1 cells, and optimum results were obtained in the presence of FCS and chloroquine at a particle ratio of 80. These nanoparticles were tested for their ability to transfer genes in vivo in the mouse lung, and a two-times increase in the expression levels was found with silica particles in comparison to EGFP alone. Very low or no cell toxicity was observed, suggesting silica nanoparticles as potential alternatives for gene transfection.