利用聚乙烯亚胺的自组装纳米粒子形成衍生物,shrna介导CD200的敲除

IF 1.4 Q4 NANOSCIENCE & NANOTECHNOLOGY
B. Khalvati, A. Dehshahri
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引用次数: 1

摘要

目的:shrna介导的沉默策略被认为是一种有效的治疗方法。本研究旨在评估先前制备的聚乙烯亚胺(PEI)衍生物对慢性淋巴细胞白血病(CLL)患者细胞中CD200基因shRNA敲除的能力。材料和方法:由于有一些关于CD200过表达在几种恶性肿瘤(如CLL)进展中的作用的研究,因此使用琥珀酰化PEI和编码抗CD200 shRNA的质粒制备了多聚物。我们评估了纳米颗粒在蛋白和mRNA水平上沉默CD200的能力,以及未经修饰的PEI及其衍生物诱导的细胞凋亡效应。结果:用PEI的伯胺偶联琥珀酸降低了聚合物的细胞毒性。在这种情况下,经修饰PEI纳米颗粒处理后,92.1%的细胞存活。此外,CD200敲除评估表明,从CLL患者获得的样本中,该基因的表达减少了50%,而对从健康供者获得的细胞使用相同的配方,CD200+细胞的表达减少了10%。在mRNA水平上对CD200进行沉默的结果显示,相对于转染无效的重组shRNA的细胞,该shRNA制剂可使患者细胞中的CD200水平降低3.2-6.06倍。结论:我们的研究结果支持琥珀酰化PEI在未来开发用于基因治疗的纳米载体中下调CD200基因的应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ShRNA-mediated knock-down of CD200 using the self-assembled nanoparticle-forming derivative of polyethylenimine
Objective(s): ShRNA-mediated silencing strategy is considered to be a potent therapeutic approach. The present study aimed to assess the ability of the previously prepared polyethylenimine (PEI) derivative for the shRNA knock-down of the CD200 gene on the cells obtained from the patients with chronic lymphocytic leukemia (CLL). Materials and Methods: Since there are several investigations regarding the role of CD200 over-expression in the progression of several malignancies (e.g., CLL), polyplexes were prepared using succinylated PEI and the plasmid encoding anti-CD200 shRNA. The ability of the nanoparticles for CD200 silencing at the levels of protein and mRNA, as well as the apoptotic effects induced by unmodified PEI and its derivative, were evaluated. Results: Conjugation of succinic acid using the primary amines of PEI reduced the cell-induced toxicity of the polymer. Under such circumstances, 92.1% of the cells remained alive after treatment with the nanoparticles based on modified PEI. In addition, CD200 knock-down evaluations demonstrated a 50% reduction in the expression of the gene in the samples obtained from patients with CLL, while using the same formulation on the cells obtained from healthy donors decreased the CD200+ cells up to 10%. The results of CD200 silencing at the mRNA level revealed that the shRNA formulation could reduce the CD200 level in the cells of the patients by 3.2-6.06-fold relative to the cells transfected with non-effective, scrambled shRNA. Conclusion: Our findings supported the application of succinylated PEI for the down-regulation of the CD200 gene in the upcoming attempts to develop nano-carriers for gene therapy.
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来源期刊
Nanomedicine Journal
Nanomedicine Journal NANOSCIENCE & NANOTECHNOLOGY-
CiteScore
3.40
自引率
0.00%
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审稿时长
12 weeks
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