Synthesis of double‐hydrophilic block copolymers via combination of oxyanion‐initiated polymerization and polymer reaction for fabricating magnetic target gene carrier

Synthesis of double‐hydrophilic block copolymers via combination of oxyanion‐initiated polymerization and polymer reaction for fabricating magnetic target gene carrier
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DOI:
10.1002/pola.24851
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发表时间:
2011-09
期刊:
Journal of Polymer Science Part A
影响因子:
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通讯作者:
Shihua Zhang;Zixu Gu;Ying Hao;Ming-zu Zhang;P. Ni
Shihua Zhang;Zixu Gu;Ying Hao;Ming-zu Zhang;P. Ni
中科院分区:
其他
文献类型:
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作者:
Shihua Zhang;Zixu Gu;Ying Hao;Ming-zu Zhang;P. Ni

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在这项工作中,我们通过氧阴离子引发聚合和聚合物反应的结合合成了一个聚阳离子和一个聚阴离子,然后开发了一种新的方法,以磁性fe3o4纳米颗粒为核心,聚乙二醇(PEG)片段为电冕,通过层接层(LbL)组装和壳交联制备可控磁性靶基因载体。磁性纳米颗粒(MNPs)首先被聚[2‐(二甲氨基)甲基丙烯酸乙酯](PDMAEMA)通过自由基聚合修饰。所得MNPs通过LbL组装用于致密脱氧核糖核酸(DNA),包括四个步骤:(1)DNA与MNPs表面的多阳离子PDMAEMA结合;(2)步骤1中产生的带负电荷的粒子与额外的聚阳离子乙氧基端帽PDMAEMA (EtO‐PDMAEMA)均聚物相互作用,形成带正电荷的表面;(3)利用二嵌段共聚物(MePEG2000‐b‐PMAASH)中聚甲基丙烯酸(PMAA)的羧基(‐COO‐)作为聚阴离子,在PMAA段中具有部分巯基(‐SH),与步骤2中产生的颗粒相互作用;(4)通过氧化MePEG2000 - b - pmaash2的- SH基团形成二硫键,复合纳米颗粒的壳被交联(S - 5s)。通过琼脂糖凝胶阻滞实验和zeta电位测定对LbL的组装过程进行了研究。它们的细胞毒性分析证明了多离子/DNA MNPs作为基因载体具有优异的性能和潜在的应用前景。©2011 Wiley期刊公司高分子材料学报,2011
In this work, we have synthesized a polycation and a polyanion via a combination of oxyanion‐initiated polymerization and polymer reaction, and then developed a novel approach to prepare a controlled magnetic target gene carrier with magnetic Fe3O4nanoparticles as core and poly(ethylene glycol) (PEG) segment as corona via layer‐by‐layer (LbL) assembly and shell‐crosslinking. Magnetic nanoparticles (MNPs) were first modified by poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA) via radical polymerization. The resulting MNPs were used to compact deoxyribonucleic acid (DNA) through LbL assembly, involving four steps: (1) the binding of DNA to the polycation PDMAEMA on the surface of MNPs; (2) the produced particles in Step 1 with negative charge interacting with additional polycation ethoxy group end‐capped PDMAEMA (EtO‐PDMAEMA) homopolymer, leading to a positive charge surface; (3) using carboxyl group (‐COO‐) of poly(methacrylic acid) (PMAA) in a diblock copolymer (MePEG2000‐b‐PMAASH) as polyanion, which has partial mercapto groups (‐SH) in PMAA segment, to interact with the particles produced in Step 2; (4) the shell of the composite nanoparticle was crosslinked by oxidizing the ‐SH groups of the MePEG2000‐b‐PMAASHto form disulfide linkage (SS). All the processes of LbL assembly were investigated by agarose gel retardation assay and zeta potential measurements. Thein vitrocytotoxicity analysis proves that polyions/DNA MNPs have excellent properties and potential applications as gene carriers. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011