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Amphiphilic polymers formed from ring-opening polymerization: a strategy for the enhancement of gene delivery

机译:由开环聚合形成的两亲聚合物:增强基因递送的策略

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摘要

Cationic liposomes and polymers are both important candidates for use as non-viral gene vectors. However, both of them have special shortcomings and application limits. This work is devoted to the combination of advantages of liposomes and polymers. The ring-opening polymerization strategy was used for the preparation of amphiphilic polymers from cyclen-based cationic small lipids. The non-hydrophobic polymer and the corresponding lipids were also prepared for performing structure-activity relationship studies. Gel electrophoresis results reveal that both the lipopolymers and liposomes could effectively condense DNA into nanoparticles and protect DNA from degradation. Compared to polymers, the DNA binding ability of liposomes is more affected by hydrophobic tails. Under the same dosage, the synthetic polymers have stronger DNA binding ability than the liposomes. In vitro transfection experiments show that the polymers could give better transfection efficiency, which was much higher than those of the corresponding liposomes and non-hydrophobic polymer. The oleyl moiety is suitable for lipidic vectors, but things were different for polymers. Under optimized conditions, up to 14.2 times higher transfection efficiency than that for 25 kDa bPEI could be obtained. More importantly, the lipopolymers showed much better serum tolerance, which was further confirmed by protein adsorption, gel electrophoresis, flow cytometry, and CLSM assays. The results indicate that ring-opening polymerization is a promising strategy for the enhancement of the gene delivery efficiency and biocompatibility of cationic lipids.
机译:阳离子脂质体和聚合物是用作非病毒基因载体的重要候选者。然而,他们两个都有特殊的缺点和应用限制。这项工作致力于脂质体和聚合物的优点的组合。开环聚合策略用于制备来自环弯基阳离子小脂质的两亲性聚合物。还制备非疏水聚合物和相应的脂质用于进行结构 - 活性关系研究。凝胶电泳结果表明,脂质聚合物和脂质体都可以将DNA有效地凝结到纳米颗粒中并保护DNA免于降解。与聚合物相比,脂质体的DNA结合能力较为受疏水性尾部的影响。在相同的剂量下,合成聚合物具有比脂质体更强的DNA结合能力。体外转染实验表明,聚合物可以提供更好的转染效率,其远高于相应的脂质体和非疏水性聚合物的转染效率。油炸部分适用于脂质载体,但对于聚合物而言是不同的。在优化条件下,转染效率高达14.2倍,而不是25 kda bpei。更重要的是,脂肪聚合物显示出更好的血清耐受性,通过蛋白质吸附,凝胶电泳,流式细胞术和Clsm测定进一步证实。结果表明,开环聚合是提高阳离子脂质的基因输送效率和生物相容性的有希望的策略。

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  • 来源
    《Biomaterials Science》 |2017年第4期|共12页
  • 作者单位

    Sichuan Univ Coll Chem Key Lab Green Chem &

    Technol Minist Educ Chengdu 610064 Peoples R China;

    Sichuan Univ Coll Chem Key Lab Green Chem &

    Technol Minist Educ Chengdu 610064 Peoples R China;

    Sichuan Univ Coll Chem Key Lab Green Chem &

    Technol Minist Educ Chengdu 610064 Peoples R China;

    Sichuan Univ Coll Chem Key Lab Green Chem &

    Technol Minist Educ Chengdu 610064 Peoples R China;

    Sichuan Univ Coll Chem Key Lab Green Chem &

    Technol Minist Educ Chengdu 610064 Peoples R China;

    Sichuan Univ Coll Chem Key Lab Green Chem &

    Technol Minist Educ Chengdu 610064 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
  • 关键词

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