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负载他莫昔芬的L-赖氨酸包被磁性氧化铁纳米颗粒在细胞周期阻滞及乳腺癌治疗抗癌活性方面具有高效性。

High efficacy of tamoxifen-loaded L-lysine coated magnetic iron oxide nanoparticles in cell cycle arrest and anti-cancer activity for breast cancer therapy.

作者信息

Rostami Soheila, Tafvizi Farzaneh, Kheiri Manjili Hamid Reza

机构信息

Department of Biology, Parand Branch, Islamic Azad University, Parand, Iran.

Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

出版信息

Bioimpacts. 2022;12(4):301-313. doi: 10.34172/bi.2021.23337. Epub 2021 Dec 1.

DOI:10.34172/bi.2021.23337
PMID:35975200
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9376161/
Abstract

Due to the side effects of drugs, the development of nanoscale drug delivery systems has led to a significant improvement in medicinal therapies due to drug pharmacokinetics changes, decreased toxicity, and increased half-life of the drug. This study aimed to synthesize tamoxifen (TMX)-loaded L-lysine coated magnetic iron oxide nanoparticles as a nano-carrier to investigate its cytotoxic effects and anti-cancer properties against MCF-7 cancer cells. Magnetic FeO nanoparticles were synthesized and coated with L-lysine (F-Lys NPs). Then, TMX was loaded onto these NPs. The characteristics of synthesized nanoparticles (F-Lys-TMX NPs) were evaluated by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), differential scanning calorimetry (DSC), vibrating sample magnetometer (VSM), and thermogravimetric analysis (TGA). The drug release was analyzed at pH 5.8 and pH 7.4. The MCF-7 cells were exposed to F-Lys-TMX NPs, F-Lys NPs, and TMX for 24, 48, and 72 hours. To evaluate the cytotoxic potential of designed nanoparticles, MTT and apoptosis assays, real-time PCR, and cell cycle analysis was carried out. The F-Lys-TMX NPs had spherical morphology with a size ranging from 9 to 30 nm. By increasing the nanoparticles concentration and treatment time, more cell proliferation inhibition and apoptosis induction were observed in F-Lys-TMX NPs-treated cells compared to the TMX. The expression levels of ERBB2, cyclin D1, and cyclin E genes were down-regulated and expression levels of the caspase-3 and caspase-9 genes were up-regulated. Studies on the drug release revealed a slow and controlled pH-dependent release of the nanoparticles. Cell cycle analysis indicated that F-Lys-TMX NPs could arrest the cells at the G0/G1 phase. The findings suggest that F-Lys-TMX NPs are more effective and have the potential for cell proliferation inhibition and apoptosis induction compared to the TMX. Hence, F-Lys-TMX NPs can be considered as an anti-cancer agent against MCF-7 breast cancer cells.

摘要

由于药物的副作用，纳米级药物递送系统的发展因药物药代动力学的改变、毒性降低和药物半衰期延长而使药物治疗有了显著改善。本研究旨在合成负载他莫昔芬（TMX）的L-赖氨酸包被的磁性氧化铁纳米颗粒作为纳米载体，以研究其对MCF-7癌细胞的细胞毒性作用和抗癌特性。合成磁性FeO纳米颗粒并用L-赖氨酸包被（F-Lys NPs）。然后，将TMX负载到这些纳米颗粒上。通过X射线衍射（XRD）、傅里叶变换红外光谱（FTIR）、扫描电子显微镜（SEM）、透射电子显微镜（TEM）、动态光散射（DLS）、差示扫描量热法（DSC）、振动样品磁强计（VSM）和热重分析（TGA）对合成的纳米颗粒（F-Lys-TMX NPs）的特性进行评估。在pH 5.8和pH 7.4条件下分析药物释放情况。将MCF-7细胞分别暴露于F-Lys-TMX NPs、F-Lys NPs和TMX中24、48和72小时。为评估所设计纳米颗粒的细胞毒性潜力，进行了MTT和凋亡检测、实时PCR以及细胞周期分析。F-Lys-TMX NPs呈球形，尺寸范围为9至30 nm。与TMX相比，随着纳米颗粒浓度的增加和处理时间的延长，在F-Lys-TMX NPs处理的细胞中观察到更多的细胞增殖抑制和凋亡诱导。ERBB2、细胞周期蛋白D1和细胞周期蛋白E基因的表达水平下调，而半胱天冬酶-3和半胱天冬酶-9基因的表达水平上调。药物释放研究表明纳米颗粒具有缓慢且受pH值影响的可控释放特性。细胞周期分析表明F-Lys-TMX NPs可使细胞停滞在G0/G1期。研究结果表明，与TMX相比，F-Lys-TMX NPs更有效且具有抑制细胞增殖和诱导凋亡的潜力。因此，F-Lys-TMX NPs可被视为一种针对MCF-7乳腺癌细胞的抗癌剂。

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[6]
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[7]
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