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阳离子固体脂质纳米粒的 pDNA 缩合能力和体外基因传递特性。

pDNA condensation capacity and in vitro gene delivery properties of cationic solid lipid nanoparticles.

机构信息

University of Modena and Reggio Emilia, Department of Pharmaceutical Sciences, Via Campi 183, 41100 Modena, Italy.

出版信息

Int J Pharm. 2010 Apr 15;389(1-2):254-61. doi: 10.1016/j.ijpharm.2010.01.030. Epub 2010 Jan 25.

Abstract

Cationic solid lipid nanoparticles (SLN) are promising nonviral gene delivery carriers suitable for systemic administration. The objective of this study was to investigate the relationship between the composition of cationic SLN and their ability to condense plasmid DNA (pDNA) and to transfer it in neuroblastoma cells. The SLN were prepared by using stearic acid and stearylamine as lipid core along with Esterquart 1 (EQ1) or Protamine obtaining two samples (SLN-EQ1 and SLN-Protamine, respectively). The cationic SLN were freeze-dried after preparation and their physical-chemical properties, including the surface composition and the transfection efficiency were investigated. The results showed that the two samples had similar size, zeta potential and pDNA binding properties but SLN-Protamine were able to condense pDNA more efficaciously than SLN-EQ1 forming smaller and less positive complexes. SLN-Protamine:pDNA complexes demonstrated to be less cytotoxic and more efficient in the transfection of Na1300 cell line than SLN-EQ1:pDNA. These findings were attributed to the different surface composition of the two samples and in particular to the localization of the Protamine on the surface of the particle while EQ1 in the lipid core. In conclusion the results here suggest that not only the z-potential but also the surface composition may affect the pDNA condensation proprieties and thus the transfection efficiency of nonviral gene nanocarriers.

摘要

阳离子固体脂质纳米粒 (SLN) 是一种很有前途的非病毒基因传递载体,适合全身给药。本研究的目的是研究阳离子 SLN 的组成与其凝聚质粒 DNA(pDNA)的能力以及在神经母细胞瘤细胞中转移的能力之间的关系。使用硬脂酸和硬脂胺作为脂质核心,与 Esterquart 1(EQ1)或鱼精蛋白一起制备 SLN,得到两种样品(SLN-EQ1 和 SLN-鱼精蛋白)。制备后,将阳离子 SLN 冷冻干燥,并研究其物理化学性质,包括表面组成和转染效率。结果表明,两种样品具有相似的粒径、Zeta 电位和 pDNA 结合特性,但 SLN-鱼精蛋白比 SLN-EQ1 更有效地凝聚 pDNA,形成更小、更负的复合物。与 SLN-EQ1:pDNA 相比,SLN-鱼精蛋白:pDNA 复合物的细胞毒性更小,对 Na1300 细胞系的转染效率更高。这些发现归因于两种样品的表面组成不同,特别是鱼精蛋白在颗粒表面的定位,而 EQ1 在脂质核心中。总之,结果表明,不仅 Zeta 电位,而且表面组成也可能影响 pDNA 凝聚特性,从而影响非病毒基因纳米载体的转染效率。

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