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Investigation of Dextran-Coated Superparamagnetic Nanoparticles for Targeted Vinblastine Controlled Release Delivery Apoptosis Induction and Gene Expression in Pancreatic Cancer Cells

机译:针对靶向长春性控制释放递送凋亡诱导和胰腺癌细胞基因表达的葡聚糖涂覆的超顺磁性纳米粒子的研究

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摘要

In the current study, the surface of superparamagnetic iron oxide (SPION) was coated with dextran (DEX), and conjugated with folic acid (FA), to enhance the targeted delivery and uptake of vinblastine (VBL) in PANC-1 pancreatic cancer cells. Numerous analyses were performed to validate the prepared FA-DEX-VBL-SPION, such as field emission scanning transmission electron microscopy, high-resolution transmission electron microscopy, dynamic light scattering (DLS), Zeta Potential, Fourier transform infrared spectroscopy, and vibrating sample magnetometry (VSM). The delivery system capacity was evaluated by loading and release experiments. Moreover, in vitro biological studies, including a cytotoxicity study, cellular uptake assessment, apoptosis analysis, and real-time PCR, were carried out. The results revealed that the obtained nanocarrier was spherical with a suitable dispersion and without visible aggregation. Its average size, polydispersity, and zeta were 74 ± 13 nm, 0.080, and −45 mV, respectively. This dual functional nanocarrier also exhibited low cytotoxicity and a high apoptosis induction potential for successful VBL co-delivery. Real-time quantitative PCR analysis demonstrated the activation of caspase-3, NF-1, PDL-1, and H-ras inhibition, in PANC-1 cells treated with the FA-VBL-DEX-SPION nanostructure. Close inspection of the obtained data proved that the FA-VBL-DEX-SPION nanostructure possesses a noteworthy chemo-preventive effect on pancreatic cancer cells through the inhibition of cell proliferation and induction of apoptosis.
机译:在目前的研究中,用葡聚糖(DEX)涂覆超顺磁性氧化铁(SPION)的表面,并与叶酸(FA)缀合,以增强在Panc-1胰腺癌细胞中的靶向输送和摄取致敏(VBL) 。进行许多分析以验证制备的FA-DEX-VBL-支线,例如场发射扫描透射电子显微镜,高分辨率透射电子显微镜,动态光散射(DLS),Zeta电位,傅里叶变换红外光谱和振动样品磁体(VSM)。通过装载和释放实验评估递送系统容量。此外,在体外生物学研究,包括细胞毒性研究,细胞摄取评估,凋亡分析和实时PCR。结果表明,所获得的纳米载体具有合适的分散体和无可见聚集的球形。其平均大小,多分散性和Zeta分别为74±13nm,0.080和-45mV。这种双官能纳米载体还表现出低细胞毒性和高凋亡诱导潜力,用于成功的VBL共同递送。实时定量PCR分析证明了用Fa-VBL-DEX- Spion纳米结构处理的PANC-1细胞中的Caspase-3,NF-1,PDL-1和H-RAS抑制的激活。所获得的数据的紧密检查证明,FA-VBL-DEX-SPION纳米结构通过抑制细胞增殖和诱导细胞凋亡来对胰腺癌细胞具有值得注意的化学预防作用。

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