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PEGylated dendrimer-entrapped gold nanoparticles with low immunogenicity for targeted gene delivery

机译:聚乙二醇化的树枝状簇夹带的金纳米颗粒,具有低免疫原性的靶向基因递送

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摘要

The high efficiency and specificity of gene therapy are mainly ascribed to the excellent transfection ability of the gene carrier. Non-viral polymer vectors have attracted extensive attention because of their low cytotoxicity and outstanding genetic loading capacity compared with viral vectors. For safe and efficient transfection of nuclear acids, here we report a novel gene delivery system, dendrimer-entrapped gold nanoparticles modified with a folate-conjugated poly (ethylene glycol) (Au DENPs-PEG-FA), possessing superior gene transfection efficiency than that of partially hydrophilic methoxy poly(ethylene glycol) (mPEG)-modified dendrimer-entrapped gold nanoparticles (Au DENPs-mPEG). The prepared Au DENPs-PEG- FA were well characterized, and our data revealed that the vector showed good cytocompatibility. Additionally, the quantification of inflammatory cytokines detected by qRT-PCR showed that the vectors displayed low innate immune response. The efficiency of nucleic acid (encoding enhanced green fluorescent protein (EGFP) and luciferase (Luc) reporter) transfection evaluated via flow cytometry and confocal microscopic imaging suggested that the Au DENPs-PEG-FA were able to transfect nucleic acid into HeLa cells with enhanced transfection efficiency. Furthermore, the existence of FA rendered the Au DENPs with excellent targeting performance via FA receptor-ligand binding interaction. The designed Au DENPs-PEG-FA with low immunogenicity and enhanced gene transfection efficiency may hold a great promise to be a superior vector for gene therapy.
机译:基因治疗的高效率和特异性主要归因于基因载体的优异转染能力。由于其与病毒载体相比,非病毒聚合物载体由于其低细胞毒性和出色的遗传负载能力而引起了广泛的关注。为了安全有效地转染核酸,在这里,我们报告了一种新的基因递送系统,用叶酸缀合的聚(乙二醇)(Au denps-peg-Fa)改性的树枝状聚合物 - 夹带的金纳米粒子,具有优异的基因转染效率部分亲水甲氧基聚(乙二醇)的(MPEG)改性树枝状聚合物包封的金纳米颗粒(金DENPs-MPEG)。制备的Au Denps-PEG-FA表征得很好,我们的数据显示载体显示出良好的细胞组合性。此外,炎性细胞因子的定量检测通过qRT-PCR结果表明,矢量显示低的先天免疫应答。核酸的效率(编码增强的绿色荧光蛋白(EGFP)和荧光素酶(LUC)报告者)通过流式细胞术和共聚焦微观成像评估的转染表明,Au denps-peg-fa能够将核酸转染到具有增强的HeLa细胞中转染效率。此外,FA的存在性通过FA受体 - 配体结合相互作用具有优异的靶向性能。具有低免疫原性和增强的基因转染效率的设计的Au Denps-PEG-FA可能具有巨大的希望成为基因治疗的优越载体。

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  • 来源
    《RSC Advances》 |2018年第3期|共9页
  • 作者单位

    Donghua Univ Coll Chem Chem Engn &

    Biotechnol Shanghai 201620 Peoples R China;

    Donghua Univ Coll Chem Chem Engn &

    Biotechnol Shanghai 201620 Peoples R China;

    Donghua Univ Coll Chem Chem Engn &

    Biotechnol Shanghai 201620 Peoples R China;

    Donghua Univ Coll Chem Chem Engn &

    Biotechnol Shanghai 201620 Peoples R China;

    Donghua Univ Coll Chem Chem Engn &

    Biotechnol Shanghai 201620 Peoples R China;

    Donghua Univ Coll Chem Chem Engn &

    Biotechnol Shanghai 201620 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
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