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首页> 外文期刊>Biomaterials Science >Redox responsive Pluronic micelle mediated delivery of functional siRNA: a modular nano-assembly for targeted delivery
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Redox responsive Pluronic micelle mediated delivery of functional siRNA: a modular nano-assembly for targeted delivery

机译：氧化还原响应Pluronic胶束介导的功能siRNA递送：针对性递送的模块化纳米组件

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摘要

There is an unmet need to develop strategies that allow site-specific delivery of short interfering RNA (siRNA) without any associated toxicity. To address this challenge, we have developed a novel siRNA delivery platform using chemically modified pluronic F108 as an amphiphilic polymer with a releasable bioactive disulfide functionality. The micelles exhibited thermoresponsive properties and showed a hydrodynamic size of similar to 291 nm in DLS and similar to 200-250 nm in SEM at 37 degrees C. The grafting of free disulfide pyridyl groups enhanced the transfection efficiency and was successfully demonstrated in human colon carcinoma (HCT116; 88%) and glioma cell lines (U87; 90%), non-cancerous human dermal fibroblast (HDF; 90%) cells as well as in mouse embryonic stem (mES; 54%) cells. To demonstrate the versatility of our modular nanocarrier design, we conjugated the MDGI receptor targeting COOP peptide on the particle surface that allowed the targeted delivery of the cargo molecules to human patent-derived primary BT-13 gliospheres. Transfection experiments with this design resulted in similar to 65% silencing of STAT3 mRNA in BT-13 gliospheres, while only similar to 20% of gene silencing was observed in the absence of the peptide. We believe that our delivery method solves current problems related to the targeted delivery of RNAi drugs for potential in vivo applications.
机译：有一个未满足的需要开发允许在没有任何相关毒性的情况下允许特异性递送短干扰RNA（siRNA）的策略。为了解决这一挑战，我们已经开发了一种新的SiRNA递送平台，其使用化学改性Pluronic F108作为具有可释放的生物活性二硫化物功能的两亲性聚合物。胶束表现出热敏性质，并且在D1中显示出类似的水动力学尺寸，并且在37摄氏度的SEM中类似于200-250nm。游离二硫酰基吡啶基的接枝增强了转染效率，并在人结肠癌中成功证明（HCT116; 88％）和胶质瘤细胞系（U87; 90％），非癌性人的皮肤成纤维细胞（HDF; 90％）细胞以及小鼠胚胎茎（MES; 54％）细胞。为了证明我们模块化纳米载波设计的多功能性，我们将靶向酸肽靶向颗粒表面上的MDGI受体缀合，允许将货物分子的靶向递送至人的专利衍生的原发性BT-13透镜。通过这种设计的转染实验导致在BT-13透视层中类似于STAT3 mRNA的65％沉默，同时在没有肽的情况下观察到20％的基因沉默。我们认为，我们的送货方式解决了与潜在的体内应用潜力有针对性的药物相关的当前问题。

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  • 来源
    《Biomaterials Science》 |2021年第11期|共6页
  • 作者

    Kadekar Sandeep; Nawale Ganesh N.; Rangasami Vignesh K.; Le Joncour Vadim; Laakkonen Pirjo; Hilborn Jons; Varghese Oommen P.; Oommen Oommen P.;

  • 作者单位

    Uppsala Univ Polymer Chem Div Dept Chem Translat Chem Biol Lab Angstrom Lab S-75121 Uppsala Sweden;

    Uppsala Univ Polymer Chem Div Dept Chem Translat Chem Biol Lab Angstrom Lab S-75121 Uppsala Sweden;

    Uppsala Univ Polymer Chem Div Dept Chem Translat Chem Biol Lab Angstrom Lab S-75121 Uppsala Sweden;

    Univ Helsinki Translat Canc Med Res Program Fac Med Helsinki Finland;

    Univ Helsinki Translat Canc Med Res Program Fac Med Helsinki Finland;

    Uppsala Univ Dept Chem Polymer Chem Angstrom Lab S-75121 Uppsala Sweden;

    Uppsala Univ Polymer Chem Div Dept Chem Translat Chem Biol Lab Angstrom Lab S-75121 Uppsala Sweden;

    Tampere Univ Fac Med &

    Hlth Technol Bioengn &

    Nanomed Grp Tampere 33720 Finland;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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