Low molecular weight polyethylenimine cross-linked by 2-hydroxypropyl-γ-cyclodextrin coupled to peptide targeting HER2 as a gene delivery vector

成果类型：

期刊论文

作者：

Huang, Hongliang;Yu, Hai;Tang, Guping;Wang, Qingqing;Li, Jun

通讯作者：

Li, J.(bielj@nus.edu.sg)

作者机构：

[Wang, Qingqing; Yu, Hai; Huang, Hongliang] Institute of Immunology, Zhejiang University, 388 Yuhangtang Road, Hangzhou, 310058, China

[Tang, Guping; Li, Jun] Division of Bioengineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore, 117574, Singapore

[Huang, Hongliang] School of Life Science, Guangdong Pharmaceutical University, 280 Waihuan East Road, Guangzhou, 510006, China

[Tang, Guping] Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, 148 Tianmoshan Road, Hangzhou, 310028, China

通讯机构：

[Li, Jun] Natl Univ Singapore, Fac Engn, Div Bioengn, 7 Engn Dr 1, Singapore 117574, Singapore.

语种：

英文

关键词：

Animal model - Animal studies - Antitumor effect - Cancer cells - Cancer gene therapy - Cationic polymers - Chemically bonded - Critical steps - Gene Delivery - Gene delivery vectors - Gene transfection - Gene vectors - High efficiency - Human epidermal growth factor - In-vitro - Low molecular weight - Molar ratio - Nonviral - Nonviral vectors - Nude mice - Oligopeptides - Ovary cancer - Plasmid DNA - Polyethylenimines - Reporter gene - Target cells - Target delivery - Therapeutic efficiency

期刊：

Biomaterials

ISSN：

0142-9612

年：

2010

卷：

31

期：

7

页码：

1830-1838

文献类别：

WOS:Article;EI:Journal article (JA)

所属学科：

ESI学科类别:材料科学;WOS学科类别:Engineering, Biomedical;Materials Science, Biomaterials

入藏号：

WOS:000274354400041;EI:20100112612714;PMID:19942284

DOI：

10.1016/j.biomaterials.2009.11.012

基金类别：

National High Technology Development Program of China [2007AA03Z355]; National Nature Science Foundation of China [30571068, 30800227]; Science and Technology Department of Zhejiang Province [20091110003]; Singapore Ministry of Education Academic Research Fund [R-397-000-031-112]; Foundation of National Excellent Doctoral Dissertation of China (FANEDD) [200364]

机构署名：

本校为其他机构

院系归属：

生命科学与生物制药学院

摘要：

Gene delivery is one of the critical steps for gene therapy. Non-viral vectors have many advantages but suffered from low gene transfection efficiency. Here, in order to develop new polymeric gene vectors with low cytotoxicity and high gene transfection efficiency, we synthesized a cationic polymer composed of low molecular weight polyethylenimine (PEI) of molecular weight of 600 Da cross-linked by 2-hydroxypropyl-γ-cyclodextrin (HP γ-CD) and then coupled to MC-10 oligopeptide containing a sequence of Met-Ala-Arg-Ala-Lys-Glu. The oligopeptide can target to HER2, the human epidermal growth factor receptor 2, which is often over expressed in many breast and ovary cancers. The new gene vector was expected to be able to target delivery of genes to HER2 positive cancer cells for gene therapy. The new gene vector was composed of chemically bonded HP γ-CD, PEI (600 Da), and MC-10 peptide at a molar ratio of 1:3.3:1.2. The gene vector could condense plasmid DNA at an N/P ratio of 6 or above. The particle size of HP γ-CD-PEI-P/DNA complexes at N/P ratios 40 was around 170-200 nm, with zeta potential of about 20 mV. The gene vector showed very low cytotoxicity, strong targeting specificity to HER2 receptor, and high efficiency of delivering DNA to target cells in vitro and in vivo with the reporter genes. The delivery of therapeutic IFN-αgene mediated by the new gene vector and the therapeutic efficiency were also studied in mice animal model. The animal study results showed that the new gene vector HP γ-CD-PEI-P significantly enhanced the anti-tumor effect on tumor-bearing nude mice as compared to PEI (25 kDa), HP γ-CD-PEI, and other controls, indicating that this new polymeric gene vector is a potential candidate for cancer gene therapy. ©2009 Elsevier Ltd. All rights reserved.

参考文献：

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