Hydrophobic poly (amino acid)-modified PEI-mediated delivery of single-chain antibody scFv1C9 inhibits HepG2 cell cycle process and xenograft growth in nude mice

Hydrophobic poly (amino acid)-modified PEI-mediated delivery of single-chain antibody scFv1C9 inhibits HepG2 cell cycle process and xenograft growth in nude mice
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疏水性聚(氨基酸)修饰的 PEI 介导的单链抗体 scFv1C9 的递送抑制裸鼠中的 HepG2 细胞周期过程和异种移植物生长。

DOI:
10.1080/09205063.2014.910153
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发表时间:
2014-06-01
影响因子:
3.6
通讯作者:
Chen, Xuesi
Chen, Xuesi
中科院分区:
工程技术4区
文献类型:
--
作者:
Fu, Chunling;Zheng, Daxue;Chen, Xuesi

文献摘要

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安全有效的基因载体是基因治疗的关键。疏水改性的Phe-PEI(PP 80)具有良好的生物相容性和基因传递能力,且体积小,易于渗透到细胞和组织中。在我们以前的工作中证明了PP 80递送rev-casp-3基因可以有效地抑制HeLa异种移植物的生长。但其作为基因载体在其他细胞或组织中的适用性有待进一步研究。本文对PP 80与质粒DNA(pDNA)的复合比例进行了定量优化,并通过家兔热原试验评价了PP 80的潜在致热原性。此外,PP 80介导的scFv 1C 9基因的表达在体外可阻断HepG 2细胞周期进程。将PP 80-scFv 1C 9注射到HepG 2裸鼠移植瘤中,可显著抑制裸鼠移植瘤的生长。进一步研究表明PP 80是一种有效的基因载体,有可能进入异种肝移植。PP 80的这些特性使其成为潜在的肿瘤基因治疗载体。
The safe and effective gene delivery vector remains the key step for gene therapy. Hydrophobic-modified Phe-PEI (PP80) was exhibited in advantage with biocompatibility and gene delivery with smaller size and easier penetration into cells and tissues. PP80 delivery of rev-casp-3 gene was demonstrated effectively to inhibit HeLa xenograft growth in our previous work. However, it was necessary to evaluate its applicability in other cells or tissues as gene carrier. Here, we quantitatively optimized the complex ratio of PP80 and plasmid DNA (pDNA) and evaluated the potential pyrogenicity by rabbit pyrogen test. In addition, PP80-mediated expression of scFv1C9 gene blocked HepG2 cell cycle progress in vitro. Subsequently, PP80-scFv1C9 was injected into HepG2 xenograft and significantly inhibited the xenograft growth in nude mice. Further investigation indicated that PP80 was an effective gene carrier and possible for entering hepatic xenograft. These features of PP80 made it attractive as a potential gene carrier for cancer therapy.