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首页> 外文期刊>Cancer letters >Hyaluronan grafted lipid-based nanoparticles as RNAi carriers for cancer cells
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Hyaluronan grafted lipid-based nanoparticles as RNAi carriers for cancer cells

机译：透明质酸植入脂质的纳米粒子作为癌细胞的RNAi载体

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RNA interference (RNAi), a natural cellular mechanism for RNA-guided regulation of gene expression could in fact become new therapeutic modality if an appropriate efficient delivery strategy that is also reproducible and safe will be developed. Numerous efforts have been made for the past eight years to address this challenge with only mild success. The majority of these strategies are based on cationic formulations that condense the RNAi payload and deliver it into the cell cytoplasm. However, most of these formulations also evoke adverse effects such as mitochondrial damage, interfering with blood coagulation cascade, induce interferon response, promote cytokine induction and activate the complement. Herein, we present a strategy that is devised from neutral phospholipids and cholesterol that self-assembled into lipid-based nanoparticles (LNPs). These LNPs were then coated with the glycosaminoglycan, hyaluronan (HA). HA-LNPs bound and internalized specifically into cancer cells compared with control, non-coated particles. Next, loaded with siRNAs against the multidrug resistance extrusion pump, p-glycoprotein (P-gp), HA-LNPs efficiently and specifically reduced mRNA and P-gp protein levels compared with control particles and with HA-LNPs loaded with control, non-targeted siRNAs. In addition, no cellular toxicity or cytokine induction was observed when these particles were cultured with human Peripheral Blood Mononuclear Cells (PBMCs). The HA-LNPs may offer an alternative approach to cationic lipid-based formulations for RNAi delivery into cancer cells in an efficient and safe manner.
机译：RNA干扰（RNAi），基因表达的RNA引导调节的天然细胞机制实际上可能成为新的治疗方式，如果也将开发可重复和安全的适当有效的交付策略。在过去的八年里，已经努力解决了这一挑战，只有轻度成功。这些策略中的大多数是基于阳离子制剂，其冷凝了RNAi有效载荷并将其递送到细胞细胞质中。然而，大多数这些制剂也引起不良反应，例如线粒体损伤，干扰血液凝固级联，诱导干扰素应答，促进细胞因子诱导并激活补体。在此，我们提出了一种从中性磷脂和胆固醇中设计成脂质基纳米颗粒（LNP）的策略。然后将这些LNP涂有糖氨基甲酰甲酰氨基（HA）。与对照，非涂覆的颗粒相比，HA-LNP与癌细胞相结合并内化。接下来，与多药电阻挤出泵，P-糖蛋白（P-GP），HA-LNPS有效地和特异性降低mRNA和P-GP蛋白水平的SIRNA与对照颗粒相比，并用控制的HA-LNPS进行比较，非有针对性的sirnas。此外，当这些颗粒用人外周血单核细胞（PBMC）培养时，没有观察到细胞毒性或细胞因子诱导。 HA-LNP可以提供替代方法，以以有效和安全的方式向RNAi递送到癌细胞中的阳离子基于脂质的配方。

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  • 来源
    《Cancer letters》 |2013年第2期|共7页
  • 作者

    Landesman-MiloD.; GoldsmithM.; LeviatanBen-AryeS.; WitenbergB.; BrownE.; LeibovitchS.; AzrielS.; TabakS.; MoradV.; PeerD.;

  • 作者单位

    Laboratory of Nanomedicine Department of Cell Research and Immunology George S. Wise Faculty of;

    Laboratory of Nanomedicine Department of Cell Research and Immunology George S. Wise Faculty of;

    Laboratory of Nanomedicine Department of Cell Research and Immunology George S. Wise Faculty of;

    Laboratory of Nanomedicine Department of Cell Research and Immunology George S. Wise Faculty of;

    Laboratory of Nanomedicine Department of Cell Research and Immunology George S. Wise Faculty of;

    Harlan Biotech Israel Ltd. Kiryat Weizmann Rehovot 76326 Israel;

    Harlan Biotech Israel Ltd. Kiryat Weizmann Rehovot 76326 Israel;

    Harlan Biotech Israel Ltd. Kiryat Weizmann Rehovot 76326 Israel;

    Harlan Biotech Israel Ltd. Kiryat Weizmann Rehovot 76326 Israel;

    Laboratory of Nanomedicine Department of Cell Research and Immunology George S. Wise Faculty of;

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

    Cancer cells; Hyaluronan; Immune response; Lipid-based nanoparticles; RNAi;

    机译：癌细胞;透明质酸;免疫应答;基于脂质的纳米粒子;RNAi;

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