地塞米松偶联线性聚乙烯亚胺的合成与表征及其作为基因载体的研究。

Synthesis and characterization of dexamethasone-conjugated linear polyethylenimine as a gene carrier.

机构信息

Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Korea.

出版信息

J Cell Biochem. 2010 Jun 1;110(3):743-51. doi: 10.1002/jcb.22587.

PMID:20512934

Abstract

Linear polyethylenimine (25 kDa, LPEI25k) has been shown to be an effective non-viral gene carrier with higher transfection and lower toxicity than branched polyethylenimine (BPEI) of comparable molecular weight. In this study, dexamethasone was conjugated to LPEI25k to improve the efficiency of gene delivery. Dexamethasone is a synthetic glucocorticoid receptor ligand. Dexamethasone-conjugated LPEI25k (LPEI-Dexa) was evaluated as a gene carrier in various cells. Gel retardation assays showed that LPEI-Dexa completely retarded plasmid DNA (pDNA) at a 0.75:1 weight ratio (LPEI/pDNA). LPEI-Dexa had the highest transfection efficiency at a 2:1 weight ratio (LPEI-Dexa/DNA). At this ratio, the size of the LPEI-Dexa/pDNA complex was approximately 125 nm and the zeta potential was 35 mV. LPEI-Dexa had higher transfection efficiency than LPEI and Lipofectamine 2000. In addition, the cytotoxicity of LPEI-Dexa was much lower than that of BPEI (25 kDa, BPEI25k). In conclusion, LPEI-Dexa has a high transfection efficiency and low toxicity and can therefore be used for non-viral gene delivery.

摘要

线性聚乙烯亚胺（25 kDa，LPEI25k）已被证明是一种有效的非病毒基因载体，与分子量相当的支化聚乙烯亚胺（BPEI）相比，具有更高的转染效率和更低的毒性。在这项研究中，将地塞米松与 LPEI25k 缀合以提高基因传递的效率。地塞米松是一种合成糖皮质激素受体配体。地塞米松缀合的 LPEI25k（LPEI-Dexa）被评估为各种细胞中的基因载体。凝胶阻滞实验表明，LPEI-Dexa 在 0.75:1 的重量比（LPEI/pDNA）下完全阻滞质粒 DNA（pDNA）。LPEI-Dexa 在 2:1 的重量比（LPEI-Dexa/DNA）下具有最高的转染效率。在这个比例下，LPEI-Dexa/pDNA 复合物的大小约为 125nm，zeta 电位为 35mV。LPEI-Dexa 的转染效率高于 LPEI 和 Lipofectamine 2000。此外，LPEI-Dexa 的细胞毒性远低于 BPEI（25 kDa，BPEI25k）。总之，LPEI-Dexa 具有高转染效率和低毒性，因此可用于非病毒基因传递。