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用于喉癌靶向基因递送的肽GE11-聚乙二醇-聚乙烯亚胺

Peptide GE11-Polyethylene Glycol-Polyethylenimine for targeted gene delivery in laryngeal cancer.

作者信息

Ren Henglei, Zhou Liang, Liu Min, Lu Weiyue, Gao Chunli

机构信息

Department of Otolaryngology-Head and Neck Surgery, Eye and ENT Hospital, Fudan University, 83 FenYang Road, Shanghai, 200031, China.

出版信息

Med Oncol. 2015 Jul;32(7):185. doi: 10.1007/s12032-015-0624-9. Epub 2015 May 26.

DOI:10.1007/s12032-015-0624-9
PMID:26008151
Abstract

The objective of this study was to evaluate the possibility of using GE11-polyethylene glycol-polyethylenimine (GE11-PEG-PEI) for targeted gene delivery to treat epidermal growth factor receptor (EGFR)-overexpressing laryngeal cancer. This study described the design, characterization, and in vitro and in vivo study of the nanocarrier GE11-PEG-PEI for gene delivery to treat laryngeal cancer. Analysis of the sizes and zeta potentials indicated that the formation of PEGylated complexes was dependent on the N/P ratio, and these complexes were capable of binding plasmid DNA and condensing DNA into small positively charged nanoparticles. The results also revealed that GE11-PEG-PEI had a weaker effect on cell survival in vitro. Gene transfection was performed on human laryngeal cancer Hep-2 cells in vitro and in vivo. Both the in vitro and in vivo results demonstrated that GE11-PEG-PEI had greater transfection efficiency than mPEG-PEI. Compared with mPEG-PEI/pORF-hTRAIL and saline, GE11-PEG-PEI/pORFh-TRAIL significantly (p < 0.05) reduced tumor growth in nude mice with laryngeal cancer. Moreover, the GE11-PEG-PEI/pORF-hTRAIL-treated groups showed more apoptosis than the mPEG-PEI/pORF-hTRAIL-treated groups. Therefore, our results showed that the peptide GE11 conjugated to PEG-PEI delivered significantly more genes to EGFR-overexpressing laryngeal cancer cells in vivo, indicating that GE11-PEG-PEI may be a suitable gene vector for treating EGFR-overexpressing laryngeal cancer.

摘要

本研究的目的是评估使用GE11-聚乙二醇-聚乙烯亚胺(GE11-PEG-PEI)进行靶向基因递送以治疗表皮生长因子受体(EGFR)过表达的喉癌的可能性。本研究描述了用于基因递送治疗喉癌的纳米载体GE11-PEG-PEI的设计、表征以及体外和体内研究。对尺寸和zeta电位的分析表明,聚乙二醇化复合物的形成取决于N/P比,并且这些复合物能够结合质粒DNA并将DNA浓缩成带正电的小纳米颗粒。结果还显示,GE11-PEG-PEI在体外对细胞存活的影响较弱。在人喉癌Hep-2细胞上进行了体外和体内基因转染。体外和体内结果均表明,GE11-PEG-PEI的转染效率高于mPEG-PEI。与mPEG-PEI/pORF-hTRAIL和生理盐水相比,GE11-PEG-PEI/pORFh-TRAIL显著(p<0.05)降低了喉癌裸鼠的肿瘤生长。此外,GE11-PEG-PEI/pORF-hTRAIL处理组比mPEG-PEI/pORF-hTRAIL处理组显示出更多的细胞凋亡。因此,我们的结果表明,与PEG-PEI偶联的肽GE11在体内向EGFR过表达的喉癌细胞递送了显著更多的基因,表明GE11-PEG-PEI可能是治疗EGFR过表达喉癌的合适基因载体。

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