Alkylimidazolium End-Modified Poly(ethylene glycol) To Form the Mono-ion Complex with Plasmid DNA for in Vivo Gene Delivery
Alkylimidazolium End-Modified Poly(ethylene glycol) To Form the Mono-ion Complex with Plasmid DNA for in Vivo Gene Delivery
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DOI：
10.1021/bm401902j
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发表时间：
2014-03-01
影响因子：
6.2
通讯作者：
Kawakami, Hiroyoshi
中科院分区：
文献类型：
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作者：
Asayama, Shoichiro;Nohara, Atsushi;Kawakami, Hiroyoshi
在这项研究中，我们认为体内多阳离子转染活性的下降，与体外相比，是由于它们的多离子复合物的形成。也就是说，由于多阳离子与质粒dna （pDNAs）之间的交联，体内基因传递的缺点主要源于难以在纳米尺度上控制所产生的多离子复合物的性质。为了避免聚阳离子的交联，我们建立了pDNA与单离子生物相容性聚合物之间形成“单离子复合物”的概念。本文合成了烷基咪唑端修饰聚乙二醇，即R-Im-PEG，并根据烷基链的长度调整了烷基咪唑基与pDNA磷酸基之间的静电相互作用，从而与pDNA形成“单离子复合物”，用于体内基因传递。我们最初的概念是由Bu-Im-PEG和pDNA组成的“单离子复合物”，而不是多离子复合物，有望为突破体内基因传递的障碍提供独特的工具。与基因传递领域一样，这项研究被认为打破了常识，即在生物大分子修饰的所有领域，在水条件下不可能形成多离子复合物，而是“单离子复合物”。
In this study, we consider that the decrease in the transfection activity of polycations in vivo, compared with that in vitro, results from their polyion complex formation. Namely, owing to cross-linking between polycations and plasmid DNAs (pDNAs), the disadvantage of in vivo gene delivery mainly stems from the difficulty in controlling the properties of the resulting polyion complex at the nanoscale size. To avoid the cross-linking by polycations, we have establish the concept of "mono-ion complex" formation between pDNA and a monocationic biocompatible polymer. Here we have synthesized alkylimidazolium end-modified poly(ethylene glycol), that is, R-Im-PEG, and have tuned the electrostatic interaction between the resulting alkylimidazolium group and the phosphate group of pDNA by the length of the alkyl chain to achieve "mono-ion complex" formation with pDNA for in vivo gene delivery. Instead of a polyion complex, our original concept of the "mono-ion complex" consisting of the Bu-Im-PEG and pDNA is expected to offer unique tools to break through the barriers of in vivo gene delivery. As well as the field of gene delivery, this study is considered to have exploded the common sense that it is impossible to form not a polyion complex but a "mono-ion complex" under aqueous conditions for all fields of the modification of biomacromolecules.