Polyetherimide-grafted Fe₃O₄@SiO2₂ nanoparticles as theranostic agents for simultaneous VEGF siRNA delivery and magnetic resonance cell imaging.
Polyetherimide-grafted Fe₃O₄@SiO2₂ nanoparticles as theranostic agents for simultaneous VEGF siRNA delivery and magnetic resonance cell imaging.
复制标题
聚醚酰亚胺接枝 Fe3O4@SiO2 纳米粒子作为同时 VEGF siRNA 递送和磁共振细胞成像的治疗诊断剂
DOI：
10.2147/ijn.s85095
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发表时间：
2015
影响因子：
8
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Li T;Shen X;Chen Y;Zhang C;Yan J;Yang H;Wu C;Zeng H;Liu Y
设计一种安全、高效的RNA干扰传递系统是基因治疗成功的关键。在这项研究中，我们设计了一种新型的聚乙烯亚胺（PEI）修饰的Fe3O4@SiO2纳米载体系统，它允许高效负载VEGF小发夹（sh）RNA，形成Fe3O4@SiO2/PEI/VEGF shRNA纳米复合物，用于VEGF基因沉默以及磁共振（MR）成像。测定了其大小、形态、颗粒稳定性、磁性、基因结合能力和保护作用。对人红细胞的低细胞毒性和溶血性表明多功能纳米复合材料具有良好的生物相容性，也没有观察到明显的凝血。纳米复合材料在室温下保持其超顺磁性，即使在PEI改性后，磁性也没有明显变化。通过普鲁士蓝染色和电感耦合等离子体原子发射光谱（ICP-AES）对MCF-7人乳腺癌细胞的细胞内化进行定性和定量分析，结果表明Fe3O4@SiO2/PEI/VEGF shRNA纳米复合物可被MCF-7细胞容易地内化，并对VEGF基因表达具有显著的抑制作用。此外，MR细胞图像显示，我们的Fe3O4@SiO2/PEI/VEGF shRNA纳米复合材料的超顺磁性氧化铁核心也可以用作癌症MR成像的T2加权造影剂。我们的数据突出了多功能Fe3O4@SiO2/PEI/VEGF shRNA纳米复合物作为同时基因递送和MR细胞成像的潜在平台，这在未来有望作为癌症治疗和诊断的治疗诊断剂。
Engineering a safe and high-efficiency delivery system for efficient RNA interference is critical for successful gene therapy. In this study, we designed a novel nanocarrier system of polyethyleneimine (PEI)-modified Fe3O4@SiO2, which allows high efficient loading of VEGF small hairpin (sh)RNA to form Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites for VEGF gene silencing as well as magnetic resonance (MR) imaging. The size, morphology, particle stability, magnetic properties, and gene-binding capacity and protection were determined. Low cytotoxicity and hemolyticity against human red blood cells showed the excellent biocompatibility of the multifunctional nanocomposites, and also no significant coagulation was observed. The nanocomposites maintain their superparamagnetic property at room temperature and no appreciable change in magnetism, even after PEI modification. The qualitative and quantitative analysis of cellular internalization into MCF-7 human breast cancer cells by Prussian blue staining and inductively coupled plasma atomic emission spectroscopy analysis, respectively, demonstrated that the Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites could be easily internalized by MCF-7 cells, and they exhibited significant inhibition of VEGF gene expression. Furthermore, the MR cellular images showed that the superparamagnetic iron oxide core of our Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites could also act as a T2-weighted contrast agent for cancer MR imaging. Our data highlight multifunctional Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites as a potential platform for simultaneous gene delivery and MR cell imaging, which are promising as theranostic agents for cancer treatment and diagnosis in the future.