Preparation and Characterization of Folate-Targeted Fe3O4 Nanoparticle Codelivering Cisplatin and TFPI-2 Plasmid DNA for Nasopharyngeal Carcinoma Therapy
Preparation and Characterization of Folate-Targeted Fe3O4 Nanoparticle Codelivering Cisplatin and TFPI-2 Plasmid DNA for Nasopharyngeal Carcinoma Therapy
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用于鼻咽癌治疗的叶酸靶向 Fe3O4 纳米颗粒共递送顺铂和 TFPI-2 质粒 DNA 的制备和表征
DOI：
10.1155/2017/2849801
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发表时间：
2017-12
影响因子：
--
通讯作者：
Minqiang Xie
中科院分区：
文献类型：
--
作者：
Juan Zhang;Huanhuan Weng;Xiangwan Miao;Quanming Li;Siqi Wang;Huifen Xie;Tao Liu;Minqiang Xie
构建了一种新的叶酸（FA）受体靶向超顺磁性Fe3O4纳米颗粒（SPIONs）共递送顺铂（CDDP）和组织因子途径抑制剂-2 （TFPI-2）质粒DNA （pDNA）。核壳纳米复合材料（FA-PEG-PEI@SPION-CDDP-TFPI-2）由超顺磁性的Fe3O4核与CDDP结合，TFPI-2壳与叶酸-聚乙二醇-聚乙烯亚胺（FA-PEG-PEI）通过静电相互作用结合。通过酰胺化反应和静电吸附合成含有FA-PEG-PEI和TFPI-2质粒的壳层，用醛类海藻酸钠修饰含有SPION-CDDP的核层。FA-PEG-PEI聚合物的质子核磁共振和傅里叶变换红外光谱显示出相应频率的各种代谢物特征峰。透射电镜图像显示FA-PEG-PEI@SPION-CDDP-TFPI-2纳米颗粒具有近单分散的球形形貌，而动态光散射研究表明其强度平均直径为149.5 nm。Zeta电位为14.89±1.83 mv，载CDDP终浓度为100 ug/ml。凝胶电泳数据显示，纳米复合材料可以保护TFPI-2 pDNA不被dna酶消化。与CNE-2细胞相比，体外普鲁士蓝铁染色和荧光分析检测到HNE-1细胞具有良好的靶向性和更高的基因转染效率（57.9%）。结果提示FA-PEG-PEI@SPION-CDDP-TFPI-2作为一种多功能抗癌纳米药物在FR阳性鼻咽癌靶向治疗中的潜在应用。
A novel folate (FA) receptor-targeted superparamagnetic Fe3O4 nanoparticles (SPIONs) codelivering cisplatin (CDDP) and tissue factor pathway inhibitor-2 (TFPI-2) plasmid DNA (pDNA) was constructed. The core shell nanocomposites (FA-PEG-PEI@SPION-CDDP-TFPI-2) were composed of superparamagnetic Fe3O4 core that binds CDDP and TFPI-2 shell that combines with folate-polyethylene glycol-polyethyleneimine (FA-PEG-PEI) via electrostatic interaction. The shell containing FA-PEG-PEI and TFPI-2 plasmid was synthesized through amidation reaction and electrostatic adsorption and the core containing SPION-CDDP was modified by aldehyde sodium alginate. Proton nuclear magnetic resonance and Fourier transform infrared spectra on FA-PEG-PEI polymers showed characteristic peaks of various metabolites in corresponding frequency. Transmission electron microscopy image of FA-PEG-PEI@SPION-CDDP-TFPI-2 nanoparticles demonstrated a near-monodisperse spherical morphology, while dynamic light scattering studies indicated an intensity-average diameter of 149.5 nm. Zeta potential was 14.89 ± 1.83 mv and the final concentration of loaded CDDP was 100 ug/ml. Gel electrophoresis data showed that the nanocomposite would protect TFPI-2 pDNA from being digested by DNases. Compared with CNE-2 cells, the good targetability and better gene transfection efficiency (57.9%) were detected by Prussian blue iron stain and fluorescence analysis in HNE-1 cells in vitro. The results suggested the potential application of FA-PEG-PEI@SPION-CDDP-TFPI-2 as a multifunctional anticancer nanomedicine on targeting therapy for FR positive NPC.
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