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首页> 外文期刊>Biomaterials Science >A one-pot modular assembly strategy for triple-play enhanced cytosolic siRNA delivery
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A one-pot modular assembly strategy for triple-play enhanced cytosolic siRNA delivery

机译：三重三相增强细胞溶质siRNA递送的单壶模块化组装策略

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摘要

Robust efficiency for cytosolic small interfering RNA (siRNA) delivery is of great importance for effective gene therapy. To significantly improve the cytosolic siRNA delivery, a one-pot modular assembly strategy is developed to assemble a triple-play enhanced cytosolic siRNA delivery system via a facile and innocuous copper-free click reaction. Specifically, three modules are prepared including octreotide for receptor-mediated endocytosis, a cell-penetrating peptide (CPP) for cell penetration, and glutamic acid for the charge-reversal property. All three modules with distinct facilitating endocytosis effects are expediently assembled on the surface of the siRNA/liposome complex to fabricate a multifunctional integrated siRNA delivery system (OCA-CC). OCA-CC has been demonstrated to have enhanced cytosolic delivery and superior gene-silencing efficiency in multiple tumor cells due to the combined effects of all the three modules. High levels of survivin-silencing are also achieved by OCA-CC on orthotopic human breast cancer (MCF-7)-bearing mice accompanied by significant tumor inhibition. This research provides a facile strategy to produce safe and tunable siRNA delivery systems for effective gene therapy and to facilitate the development of multifunctional siRNA vectors.
机译：细胞溶质小干扰RNA（siRNA）递送的鲁棒效率对于有效基因治疗具有重要意义。为了显着改善细胞溶质siRNA递送，开发了一种单壶模块化组装策略以通过容易和无害的铜咔哒反应组装三重游戏增强的细胞溶质siRNA递送系统。具体地，制备三个模块，包括用于受体介导的内吞作用的八萜苷，用于细胞渗透的细胞穿透肽（CPP）和用于电荷反转性的谷氨酸。所有三个具有不同促进内吞作用的模块在siRNA /脂质体复合物的表面上有利地组装，以制造多功能集成siRNA递送系统（OCA-CC）。由于所有三个模块的组合效应，已证明OCA-CC具有增强的细胞溶质递送和高肿瘤细胞的基因沉默效率。 OCA-CC在原位人乳腺癌（MCF-7）伴随着显着的肿瘤抑制的情况下，OCA-CC也实现了高水平的Survivin-Sulencing。本研究提供了一种体内策略，用于生产用于有效基因治疗的安全和可调的siRNA递送系统，并促进多功能siRNA载体的发展。

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  • 来源
    《Biomaterials Science》 |2019年第3期|共13页
  • 作者

    Xie Daping; Du Junjie; Bao Moxyel; Zhou Anwei; Tian Chunli; Xue Lingjing; Ju Caoyun; Shen Jian; Zhang Can;

  • 作者单位

    China Pharmaceut Univ Ctr Adv Pharmaceut &

    Biomat State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Ctr Adv Pharmaceut &

    Biomat State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Ctr Adv Pharmaceut &

    Biomat State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Ctr Adv Pharmaceut &

    Biomat State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Ctr Adv Pharmaceut &

    Biomat State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Ctr Adv Pharmaceut &

    Biomat State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Ctr Adv Pharmaceut &

    Biomat State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    Nanjing Normal Univ Jiangsu Collaborat Innovat Ctr Biomed Funct Mat Nanjing 210046 Jiangsu Peoples R China;

    China Pharmaceut Univ Ctr Adv Pharmaceut &

    Biomat State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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