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葡聚糖包覆的超顺磁性纳米粒子用于长春碱靶向控制释放、递药、诱导胰腺癌细胞凋亡和基因表达的研究。

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

机构信息

Department of Basic Sciences, College of Nursing, University of Misan, Maysan 62001, Iraq.

Faculty of Biotechnology, Al-Qasim Green University, Babylon 51013, Iraq.

出版信息

Molecules. 2020 Oct 15;25(20):4721. doi: 10.3390/molecules25204721.

Abstract

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 , , , and 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.

摘要

在本研究中,超顺磁性氧化铁(SPION)的表面涂覆有葡聚糖(DEX),并与叶酸(FA)结合,以增强长春碱(VBL)在 PANC-1 胰腺癌细胞中的靶向递送和摄取。进行了许多分析来验证制备的 FA-DEX-VBL-SPION,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强计(VSM)。通过加载和释放实验评估了递送系统的载药量。此外,还进行了体外生物学研究,包括细胞毒性研究、细胞摄取评估、细胞凋亡分析和实时 PCR。结果表明,所获得的纳米载体为球形,具有合适的分散性且没有可见的聚集。其平均粒径、多分散性和 Zeta 电位分别为 74 ± 13nm、0.080 和-45mV。这种双功能纳米载体还表现出低细胞毒性和高凋亡诱导潜力,可成功共递送 VBL。实时定量 PCR 分析表明,FA-VBL-DEX-SPION 纳米结构处理的 PANC-1 细胞中 、 、 和 的抑制被激活。仔细检查所得数据证明,FA-VBL-DEX-SPION 纳米结构通过抑制细胞增殖和诱导细胞凋亡,对胰腺癌细胞具有显著的化学预防作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c17/7587551/267bfb41a799/molecules-25-04721-g001.jpg

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