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pH-responsive polydopamine nanoparticles for photothermally promoted gene delivery

机译:用于光热促进的基因递送的pH-响应聚德米胺纳米粒子

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摘要

Recently, stimuli-responsive gene carriers have been widely studied to overcome the extra- and intracellular barriers in cancer treatment. In this study, we modified polydopamine nanoparticles with low-molecular weight polyethylenimine (PEI1.8k) and polyethylene glycol-phenylboronic acid (PEG-PBA) to prepare pH-responsive gene carrier PDANP-PEI-rPEG. PBA and polydopamine could form pH-responsive boronate ester bonds. Nonresponsive PDANP-PEI-nPEG and non-PEGylated PDANP-PEI were also studied as control. Both PDANP-PEI-rPEG/DNA and PDANP-PEI-nPEG/DNA complexes remained stable in the pH environment of blood circulation or extracellular delivery (pH 7.4) owing to the PEG modification. And after being internalized into endosomes: the boronate ester bonds could be cleaved. The pH responsive ability of PDANP-PEI-rPEG might facilitate complexes dissociation and gene release inside cells. The transfection level of PDANP-PEI-rPEG/DNA complexes was about 100 times higher than that of PDANP-PEI-nPEG/DNA complexes with the same mass ratios. Moreover, after NIR light irradiation at the power density of 2.6 W/cm(2) for 20 min, the good photothermal conversion ability of PDANP resulted in quick endosomal escape. The transfection level of PDANP-PEI-rPEG/DNA complexes doubled, even higher than that of lipofectamine 2000/DNA complexes. This was also confirmed by Bafilomycin A1 inhibition test and CISM observation. In response to the acidic pH within cancer cells and the NIR light irradiation, the PDANP-PEI-rPEG carrier could overcome multiple obstacles in gene delivery, which was promising for further application in gene therapy.
机译:最近,刺激响应性基因载体已被广泛研究以克服癌症治疗的细胞和细胞内屏障。在该研究中,我们用低分子量聚乙烯胺(PEI1.8K)和聚乙二醇 - 苯基硼酸(PEG-PBA)改性多胺纳米颗粒以制备pH-响应基因载体pdanp-pei-rpeg。 PBA和聚二胺可以形成pH响应硼酸酯键。还研究了非响应性PdanP-PEI-NPEG和非聚乙二醇化的PDANP-PEI作为对照。由于PEG改性,PdanP-PEI-RPEG / DNA和PdanP-PEI-NPEG / DNA复合物在血液循环或细胞外递送(pH7.4)的pH环境中保持稳定。在内部化到内体之后:可以裂解硼酸酯键。 PdanP-PEI-RPEG的pH响应能力可能促进复合物解离和基因释放内部细胞内。 PdanP-PEI-RPEG / DNA复合物的转染水平比具有相同质量大量的PdanP-PEI-NPEG / DNA配合物高约100倍。另外,在鼻子密度为2.6W / cm(2)的尿液照射后20分钟,PdanP的良好光热转化能力导致快速内体逸出。 PdanP-PEI-RPEG / DNA复合物的转染水平加倍,甚至高于Lipofectamine 2000 / DNA复合物的转染水平。这也得到了Bafilomycin A1抑制试验和Cism观察证实。响应于癌细胞内的酸性pH和NIR光照射,PDANP-PEI-RPEG载体可以克服基因递送中的多个障碍,这是对基因治疗的进一步应用。

著录项

  • 来源
    《Materials science & engineering》 |2020年第3期|110396.1-110396.11|共11页
  • 作者单位

    Zhejiang Univ Dept Polymer Sci & Engn MOE Key Lab Macromol Synth & Functionalizat Hangzhou 310027 Peoples R China;

    Zhejiang Univ Dept Polymer Sci & Engn MOE Key Lab Macromol Synth & Functionalizat Hangzhou 310027 Peoples R China;

    Zhejiang Univ Dept Polymer Sci & Engn MOE Key Lab Macromol Synth & Functionalizat Hangzhou 310027 Peoples R China;

    Zhejiang Univ Dept Polymer Sci & Engn MOE Key Lab Macromol Synth & Functionalizat Hangzhou 310027 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Gene delivery; Stimuli responsive; Polydopamine nanoparticles; Enhanced endosomal escape;

    机译:基因递送;刺激响应;聚二胺纳米粒子;增强的内部突变;

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