Development of lipopolyplexes for gene delivery: A comparison of the effects of differing modes of targeting peptide display on the structure and transfection activities of lipopolyplexes.
Development of lipopolyplexes for gene delivery: A comparison of the effects of differing modes of targeting peptide display on the structure and transfection activities of lipopolyplexes.
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DOI：
10.1002/psc.3131
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Tabor AB
中科院分区：
文献类型：
--
作者：
Bofinger R;Zaw-Thin M;Mitchell NJ;Patrick PS;Stowe C;Gomez-Ramirez A;Hailes HC;Kalber TL;Tabor AB
非病毒基因递送载体的设计、合成和制备是一个新的研究领域。最有效的非病毒基因递送系统是脂多糖，其中阳离子多肽与质粒DNA和脂类共同形成。脂多糖载体的一个优点是它们有可能通过在表面附着多肽靶向配体而被靶向于特定的细胞类型，从而提高了对肿瘤细胞等疾病靶点的转染率和选择性。在这篇论文中，我们研究了两种不同的方式在脂多糖表面展示细胞特异性多肽的靶向配体。将含有受体结合序列和DNA缩合序列的双峰型多肽形成的脂多聚体与靶向配体直接连接到其中一种脂类的脂多聚体进行了比较。研究了三种EGFR靶向多肽序列，以及一系列脂类制剂和马来酰亚胺的脂类结构。利用携带萤火虫荧光素酶和绿色荧光蛋白表达基因的质粒DNA，研究了脂多糖的生物物理性质及其在基底样乳腺癌细胞系中的转染率。荧光猝灭实验也被用来探测脂多糖中肽和PDNA组分的大分子组织。我们证明了两种脂多糖靶向的方法都能给出合理的转染率，并且每种脂多糖制剂的转染率都高度依赖于靶向肽的序列。为了达到最大的治疗效率，应该针对每种靶细胞类型研究不同的多肽靶向序列和脂多糖结构。
The design, synthesis and formulation of non‐viral gene delivery vectors is an area of renewed research interest. Amongst the most efficient non‐viral gene delivery systems are lipopolyplexes, in which cationic peptides are co‐formulated with plasmid DNA and lipids. One advantage of lipopolyplex vectors is that they have the potential to be targeted to specific cell types by attaching peptide targeting ligands on the surface, thus increasing both the transfection efficiency and selectivity for disease targets such as cancer cells. In this paper, we have investigated two different modes of displaying cell‐specific peptide targeting ligands at the surface of lipopolyplexes. Lipopolyplexes formulated with bimodal peptides, with both receptor binding and DNA condensing sequences, were compared with lipopolyplexes with the peptide targeting ligand directly conjugated to one of the lipids. Three EGFR targeting peptide sequences were studied, together with a range of lipid formulations and maleimide lipid structures. The biophysical properties of the lipopolyplexes and their transfection efficiencies in a basal‐like breast cancer cell line were investigated using plasmid DNA bearing genes for the expression of firefly luciferase and green fluorescent protein. Fluorescence quenching experiments were also used to probe the macromolecular organisation of the peptide and pDNA components of the lipopolyplexes. We demonstrated that both approaches to lipopolyplex targeting give reasonable transfection efficiencies, and the transfection efficiency of each lipopolyplex formulation is highly dependent on the sequence of the targeting peptide. To achieve maximum therapeutic efficiency, different peptide targeting sequences and lipopolyplex architectures should be investigated for each target cell type.
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影响因子：
4.2
作者：
Hart, SL;Arancibia-Cárcamo, CV;Kinnon, C
通讯作者：
Kinnon, C
影响因子：
4.1
作者：
Law, G. H. Erica;Gandelman, Olga A.;Murray, James A. H.
通讯作者：
Murray, James A. H.
影响因子：
14
作者：
Mitchell N;Kalber TL;Cooper MS;Sunassee K;Chalker SL;Shaw KP;Ordidge KL;Badar A;Janes SM;Blower PJ;Lythgoe MF;Hailes HC;Tabor AB
通讯作者：
Tabor AB
影响因子：
14
作者：
Fortier, Charles;De Crescenzo, Gregory;Durocher, Yves
通讯作者：
Durocher, Yves
影响因子：
4.8
作者：
Li, ZH;Zhao, RJ;Gu, JR
通讯作者：
Gu, JR