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首页> 外文期刊>Advanced Functional Materials >Polycatechol Mediated Small Interfering RNA Delivery for the Treatment of Ulcerative Colitis
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Polycatechol Mediated Small Interfering RNA Delivery for the Treatment of Ulcerative Colitis

机译：Polycatechol介导的小干扰RNA递送用于治疗溃疡性结肠炎

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摘要

Small interfering RNA (siRNA)-based therapeutics has high potency and specificity in silencing target genes for the treatment of various diseases; however, the design of efficient and safe carriers for siRNA delivery remains grand challenges. In this study, a family of cationic polycatechols are designed and synthesized using different direct polymerization methods for siRNA delivery in vitro and in vivo. It is observed that the introduction of multiple catechol moieties into cationic polymers could enhance their siRNA binding capability, thus greatly improving the biological stability, cell internalization, and gene silencing efficiency of their complexes. The flexibility of the backbone in polycatechols is also found to influence the whole siRNA delivery process. After screening, the lead cationic polycatechol P1 with a 50% catechol molar ratio could efficiently deliver siRNAs into different cell lines and downregulate various target genes even in the presence of serum proteins. Besides, P1 is also able to successfully silence tumor necrosis factor-alpha in macrophages in vitro and in vivo, and efficiently mitigate the symptoms without causing adverse effects in a dextran sodium sulfate-induced ulcerative colitis model. The results demonstrate that those polycatechols could be developed as a promising class of siRNA delivery systems for gene therapy.
机译：基于小干扰RNA（siRNA）的治疗剂在沉默的靶基因中具有高效力和特异性，用于治疗各种疾病;然而，SiRNA交付的高效和安全载体的设计仍然是大挑战。在该研究中，使用不同的直接聚合方法在体外和体内使用不同的直接聚合方法设计和合成阳离子聚碳酚系列。观察到，将多种儿茶素部分引入阳离子聚合物可以提高它们的siRNA结合能力，从而大大提高了它们配合物的生物稳定性，细胞内化和基因沉默效率。还发现骨干在聚碳酚中的柔韧性来影响整个siRNA递送过程。在筛选后，具有50％儿茶酚摩尔比的铅阳离子聚碳酚P1可以将siRNA有效地递送到不同的细胞系中，即使在血清蛋白质存在下也可以下调各种靶基因。此外，P1还能够在体外和体内在巨噬细胞中成功沉默肿瘤坏死因子-α，并有效减轻症状而不会导致葡聚糖硫酸钠诱导的溃疡性结肠炎模型中的不良反应。结果表明，这些聚碳酚可以作为基因治疗的有希望的siRNA递送系统开发。

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  • 来源
    《Advanced Functional Materials》 |2021年第24期|2101646.1-2101646.11|共11页
  • 作者

    Fan Qianqian; Yang Zhen; Li Yuhan; Cheng Yiyun; Li Yiwen;

  • 作者单位

    East China Normal Univ Sch Life Sci Shanghai Key Lab Regulatory Biol Shanghai 200241 Peoples R China;

    Sichuan Univ Coll Polymer Sci & Engn State Key Lab Polymer Mat Engn Chengdu 610065 Peoples R China;

    South China Univ Technol Sch Mol Sci & Engn South China Adv Inst Soft Matter Sci & Technol Guangzhou 510640 Peoples R China;

    East China Normal Univ Sch Life Sci Shanghai Key Lab Regulatory Biol Shanghai 200241 Peoples R China|South China Univ Technol Sch Mol Sci & Engn South China Adv Inst Soft Matter Sci & Technol Guangzhou 510640 Peoples R China;

    Sichuan Univ Coll Polymer Sci & Engn State Key Lab Polymer Mat Engn Chengdu 610065 Peoples R China;

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

    cationic polymers; polycatechol; small interfering RNA delivery; ulcerative colitis;

    机译：阳离子聚合物;聚碳酚;小干扰RNA递送;溃疡性结肠炎;

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