Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.
Bioconjug Chem. 2010 May 19;21(5):836-43. doi: 10.1021/bc900374d.
Gold nanoparticles (GNPs) conjugated with low molecular weight polyethylenimine (PEI 800 Da) were synthesized, and their characteristics as gene transfection vectors were investigated. The polyethylenimine conjugated GNPs (GNP-PEI800s) can retard plasmid DNA completely at N/P ratios above 4 in electrophoresis on agarose gel, and they also render effective protection of DNA from attack by DNase. TEM imaging revealed that GNP-PEI800s with higher PEI grafting density resulted in more compact and smaller complexes with plasmid DNA, compared to those obtained with lower grafting density ones. These complexes showed high efficiency in gene delivery in monkey kidney cells in vitro. In the absence of serum, GNP-PEI800s can transfect pGL-3 to COS-7 cells 3 to 4 orders more efficient than unmodified PEI800, reaching almost the same magnitude of PEI 25 kDa. More importantly, in contrast to the dramatically lowered efficiency of high molecular weight PEIs such as PEI 25 kDa in the presence of serum, the efficiency of GNP-PEI800s can be retained or even enhanced in serum-containing media. GNP-PEI800 1.3 exhibited transfection efficiency exceeding 60-fold that of PEI 25 kDa in 10% serum medium. All GNP-PEI800s exhibit mild cytotoxicity in comparison with that of PEI 25 kDa.
金纳米粒子(GNPs)与低分子量聚乙烯亚胺(PEI 800 Da)偶联,研究了其作为基因转染载体的特性。聚乙稀亚胺偶联的金纳米粒子(GNP-PEI800)在琼脂糖凝胶电泳中,当 N/P 比高于 4 时可以完全阻止质粒 DNA 的迁移,并且可以有效保护 DNA 免受 DNA 酶的攻击。TEM 成像显示,与较低接枝密度的 GNP-PEI800 相比,具有较高接枝密度的 GNP-PEI800 与质粒 DNA 形成更紧凑和更小的复合物。这些复合物在猴肾细胞中的体外基因传递效率很高。在没有血清的情况下,GNP-PEI800 可以将 pGL-3 转染到 COS-7 细胞中,其效率比未修饰的 PEI800 高 3 到 4 个数量级,接近 25 kDa 的 PEI 的效率。更重要的是,与高分子量的 PEI(如 25 kDa 的 PEI)在血清存在的情况下效率显著降低形成鲜明对比的是,GNP-PEI800 在含血清的培养基中的效率可以保持甚至增强。在 10%血清培养基中,GNP-PEI8001.3 的转染效率超过 25 kDa PEI 的 60 倍。与 25 kDa 的 PEI 相比,所有 GNP-PEI800 均表现出较低的细胞毒性。