Effects of cell-penetrating peptides and pegylation on transfection efficiency of polyethylenimine in mouse lungs
Effects of cell-penetrating peptides and pegylation on transfection efficiency of polyethylenimine in mouse lungs
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DOI：
10.1002/jgm.1255
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发表时间：
2008-11-01
影响因子：
3.5
通讯作者：
Kissel, Thomas
中科院分区：
文献类型：
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作者：
Nguyen, Juliane;Xie, Xiulan;Kissel, Thomas
背景细胞穿透肽(CPPs)可作为蛋白质、多肽和核酸的细胞内转运载体。本研究比较了不同的聚乙二醇化聚乙烯亚胺(PEI)在A549、CALU-3细胞和小鼠气管内给药后的转染率。方法将聚乙二醇化的聚乙二醇亚胺(PEI)通过异双官能团的聚乙二醇联接物(PEP-PEL)偶联制备偶联物，通过核磁共振和扩散有序光谱分析证实了CPP-PEP-PEL的H-1生物偶联物结构。将未修饰的PEI 25 kDa与聚乙二醇化的PEI进行比较，考察其在细胞培养上的聚集趋势、与粘蛋白的相互作用以及对肝素的稳定性。结果与未修饰的PEI 25 kDa相比，所有结合物均显示出更高的转染率。结合物的大小一般是
Background Cell-penetrating peptides (CPPs) could potentially be used as vectors for intracellular delivery of proteins, peptides and nucleic acids. The present study examined different CPPs, such as TAT-derived and arginine rich sequences, as well as model amphiphilic peptide, with respect to transfection efficiency of pegylated polyethylenimine (PEI) in A549, Calu-3 cells and in mice after intra-tracheal administration.Methods The conjugates were prepared by the coupling of CPPs to PEI via a heterobifunctional polyethylene glycol (PEG) linker, resulting in the H-1-bioconjugates CPP-PEG-PEL Structures were successfully confirmed by d nuclear magnetic resonance and diffusion-ordered spectroscopy. Unmodifie PEI 25 kDa was compared with pegylated PEI, and aggregation tendency in cell culture medium, interaction with mucin and stability against heparin was assayed. After evaluating transfection efficiency of the polymers in two different lung cell lines, luciferase reporter gene expression was determined in mouse lungs.Results All conjugates showed superior transfection efficiency compared to unmodified PEI 25 kDa. The conjugates sizes were generally