磁性纳米颗粒siRNA和依托泊苷在耐药模型MCF-7细胞上的合成及其生物活性:与MRP1酶的分子对接研究

IF 1.4 Q4 NANOSCIENCE & NANOTECHNOLOGY
S. Yalçın, U. Gündüz
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引用次数: 3

摘要

目的:本研究以MCF-7/Sensitive和MCF-7/1000Etoposide耐药细胞为研究对象,研究了siRNA和负载羟基丁酸乙二醇酯(PHB)的磁性纳米颗粒(MNPs)对MRP-1(多药耐药相关蛋白1)基因的表达水平和抗癌活性。为此,通过共沉淀法制备了PHB覆盖的氧化铁基磁性纳米颗粒(PHB-MNPs)。我们使用磁性纳米颗粒是因为它们在体内癌症治疗中包括高度靶向性的肿瘤。材料与方法:将抗癌药物依托泊苷负载于PHB-MNPs上。应用siRNA和依托泊苷负载的PHB-MNPs对癌症细胞进行体外细胞毒性分析。使用qRT-PCR显示与耐药性相关的MRP1的表达水平。在本研究中,我们还通过分子对接分析研究了纳米颗粒系统是否可以成为潜在的抗癌药物靶点。结果:依托泊苷对MCF-7/敏感细胞和MCF-7/1000Eto耐药细胞的IC50值分别为50,6μM和135,7μM。在MCF-7和MCF-7/1000 Eto细胞上,siRNA和足叶乙甙负载的PHB包被的磁性纳米颗粒的IC50值分别为10,18μM和39,21μM。根据基因表达结果,MRP1在MCF-7/1000Eto细胞中的表达上调了4倍。然而,由于应用了siRNA-Etoposide负载的磁性纳米颗粒,它被下调了约3倍。结论:根据对接结果,纳米颗粒系统可能是一种药物活性物质。这项研究的结果表明,siRNA和足叶乙甙负载的PHB覆盖的氧化铁基磁性纳米颗粒可以成为克服耐药性的潜在靶向治疗剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis and biological activity of siRNA and Etoposide with magnetic nanoparticles on drug resistance model MCF-7 Cells: Molecular docking study with MRP1 enzyme
Objective(s): In this work, MRP-1 (Multidrug resistance-associated protein 1) gene expression levels and anticancer activity of siRNA and Etoposide loaded Poly-hydroxybutyrate (PHB) coated magnetic nanoparticles (MNPs) was studied on MCF-7/Sensitive and MCF-7/1000Etoposide resistance cells. For this purpose, PHB covered iron oxide-based magnetic nanoparticles (PHB-MNPs) were prepared by coprecipitation. We used magnetic nanoparticles because they include highly targeted to tumors in vivo cancer therapy. Materials and Methods: Etoposide, anti-cancer drug, was loaded onto the PHB-MNPs. The in vitro cytotoxicity analysis of siRNA and Etoposide-loaded PHB-MNPs was applied on cancer cells. The expression levels of MRP1 related to drug resistance were shown using qRT-PCR. In the present study, we also investigated whether nanoparticle system could be a potential anticancer drug target with molecular docking analyses.Results: The IC50 values of Etoposide on MCF-7/sensitive and MCF-7/1000Eto resistance cells were identified as 50,6 μM and 135,7 μM, respectively. IC50 values of siRNA and Etoposide loaded PHB coated magnetic nanoparticles were determined as 10,18 μM and 39,21 μM on MCF-7 and MCF-7/1000 Eto cells, respectively. According to the gene expression results, MRP1 expression was 4 fold upregulated in MCF-7/1000Eto cells. However, it was about 3 fold downregulated due to the application of siRNA-Etoposide loaded magnetic nanoparticles. Conclusion: According to the docking results, nanoparticle system may be a drug active substance with obtained results. The results of this study demonstrated that siRNA and Etoposide loaded PHB covered iron oxide based magnetic nanoparticles can be a potential targeted therapeutic agent to overcome drug resistance.
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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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0
审稿时长
12 weeks
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