在 MCF-7 细胞中用阳离子纳米囊递送 siRNA 沉默 c-myc 基因。

IF 2.8 4区 医学 Q2 PHARMACOLOGY & PHARMACY Journal of Pharmacy and Pharmacology Pub Date : 2024-11-22 DOI:10.1093/jpp/rgae146
Shatha N Abdeljaber, Alaa A Aljabali, Bahaa Altrad, Mohammad A Obeid
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引用次数: 0

摘要

目的:c-myc 被认为负责超过 15%的基因调控,是细胞增殖所必需的蛋白质的转录因子。本研究旨在开发纳米载体,利用抗 c-myc 短干扰 RNA(siRNA)在 MCF-7 细胞中敲除 c-myc 的表达。由于抗 c-myc siRNA 会降解 c-myc mRNA,因此改变 c-myc 原癌基因的活性被认为是最大限度减少癌细胞生长的一个重要因素:方法:用吐温85、胆固醇和十二烷基二甲基溴化铵以50:40:10和40:40:20的摩尔比制备噪音体。将抗 c-myc siRNA 加载到制备好的 niosomes 中,然后应用于 MCF-7 细胞:主要发现:Niosomes 带有总的正电荷,与 siRNA 形成静电相互作用。niosomes呈球形,大小范围为70-100 nm。制备的niosomes对MCF-7细胞无毒,两种制剂的IC50值均大于250微克/毫升。封装抗 myc siRNA 后,nioplexes 可使 c-myc mRNA 表达量比未处理细胞减少 50%以上。空的niosomes不影响c-myc mRNA的表达水平,这表明这种效应是由siRNA而不是颗粒本身引起的:本研究证明,niosomes 可以作为 siRNA 的合适载体,用于敲除 MCF-7 细胞中的 c-myc 致癌基因,从而减少癌细胞的生长。
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Silencing c-myc gene by siRNA delivered by cationic niosomes in MCF-7 cells.

Objectives: Gene therapy has a strong potential to treat different cancer types cancers with high therapeutic outcomes. c-myc is believed to be responsible for more than 15% of all gene regulation and functions as a transcription factor for proteins essential for cell proliferation. This study aimed to develop niosome nanocarriers to knockdown c-myc expression using anti-c-myc short-interfering RNA (siRNA) in MCF-7 cells. Altering the activity of the c-myc proto-oncogene has been identified as an important element in minimizing cancer cell growth because anti-c-myc siRNA degrades c-myc mRNA.

Methods: Noisomes were prepared from Tween 85, cholesterol, and didodecyldimethylammonium bromide at 50:40:10 and 40:40:20 molar ratios. Anti-c-myc siRNA was loaded in the prepared niosomes and then applied on MCF-7 cells.

Key findings: Niosomes had a total positive charge formed electrostatic interactions with siRNA. Niosomes were spherical with a size range of 70-100 nm. The prepared niosomes were nontoxic to MCF-7 cells, with IC50 values of >250 µg/ml for both formulations. After encapsulation of anti-c-myc siRNA, nioplexes reduced c-myc mRNA expression by more than 50% compared with the untreated cells. Empty niosomes did not affect c-myc mRNA expression levels, indicating that the effect was due to siRNA rather than the particles themselves.

Conclusions: This study provides evidence that niosomes can function as suitable carriers for siRNA delivery to knockdown the c-myc oncogene in MCF-7 cells, thus reducing cancer cell growth.

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来源期刊
CiteScore
6.60
自引率
0.00%
发文量
91
审稿时长
3 months
期刊介绍: JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.
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