Biosynthesis and characterization of a novel genetically engineered polymer for targeted gene transfer to cancer cells

被引：41

作者：

Canine, Brenda F. ^{[1
]}

Wang, Yuhua ^{[1
]}

Hatefi, Arash ^{[1
]}

机构：

[1] Washington State Univ, Ctr Integrated Biotechnol, Dept Pharmaceut Sci, Pullman, WA 99164 USA

来源：

JOURNAL OF CONTROLLED RELEASE | 2009年 / 138卷 / 03期

关键词：

Biopolymer; Genetically engineered polymer; Biomimetic vector; Non-viral vector; Gene therapy; PORE COMPLEX COMPOSITION; REDUCIBLE POLYCATIONS; NUCLEIC-ACIDS; PROTEIN; DELIVERY; EFFICIENT; NANOCARRIERS; TRANSPORT; VECTORS; PEPTIDE;

D O I：

10.1016/j.jconrel.2009.04.017

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A novel multi-domain biopolymer was designed and genetically engineered with the purpose to target and transfect cancer cells. The biopolymer contains at precise locations: 1) repeating units of arginine and histidine to condense pDNA and lyse endosome membranes, 2) a HER2 targeting affibody to target cancer cells, 3) a pH responsive fusogenic peptide to destabilize endosome membranes and enhance endosomolytic activity of histidine residues, and 4) a nuclear localization signal to enhance translocation of pDNA towards the cell nucleus. The results demonstrated that the biopolymer was able to condense pDNA into nanosize particles, protect pDNA from serum endonucleases, target HER2 positive cancer cells but not HER2 negative ones, efficiently disrupt endosomes, and effectively reach the cell nucleus of target cells to mediate gene expression. To reduce potential toxicity and enhance biodegradability, the biopolymer was designed to be susceptible to digestion by endogenous furin enzymes inside the cells. The results revealed no significant biopolymer related toxicity as determined by impact on cell viability. Published by Elsevier B.V.

引用

页码：188 / 196

页数：9

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