SPIO-loaded nanostructured lipid carriers as liver-targeted molecular T2-weighted MRI contrast agent.
SPIO-loaded nanostructured lipid carriers as liver-targeted molecular T2-weighted MRI contrast agent.
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DOI：
10.21037/qims.2018.09.03
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发表时间：
2018-07
影响因子：
2.8
通讯作者：
Xiuliang Zhu;Xue-Ying Deng;Chen-ying Lu;Ying Chen;Liyong Jie;Qian Zhang;Wei Li;Zuhua Wang
中科院分区：
文献类型：
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作者：
Xiuliang Zhu;Xue-Ying Deng;Chen-ying Lu;Ying Chen;Liyong Jie;Qian Zhang;Wei Li;Zuhua Wang
背景超顺磁性氧化铁(SPIO)是磁共振成像(MRI)中的一种负性造影剂，广泛应用于临床，包括肝脏疾病的诊断。肝细胞靶向磁共振造影剂(MRCA)可以为肝脏疾病的评估提供有用的信息。我们制备了靶向磁性纳米脂质载体(MNLC)，以提高肝细胞的靶向效率。方法用透射电子显微镜观察MNLCs的体外特性。采用四甲基偶氮唑蓝(四甲基偶氮唑蓝)比色法测定MNLCs的细胞毒作用。采用共聚焦显微镜、流式细胞仪和磁共振成像等方法进行体外检测。通过体内荧光成像和MRI检测MNLCs增强的肝靶向效率。结果成功制备了Gal-NLC-SPIO。MNLC的细胞毒性实验表明，MNLC对LO2细胞具有较低的细胞毒性和较高的生物相容性。更重要的是，我们证实了Gal-NLC-SPIO在体外被LO2细胞摄取的能力高于Gal-NLC-SPIO/PEG和游离Gal。正常小鼠肝脏MNLC的分布研究表明，Gal-NLC-SPIO对肝脏的荧光强度明显强于NLC-SPIO和Gal-NLC-SPIO/fi。Gal-NLC-SPIO的肝靶向效率在体内和体外均得到证实。结论成功制备了肝靶向MNLCs，显示了准确的肝细胞靶向，有望成为一种新的MRI对比剂，用于肝脏疾病的诊断。
Background Superparamagnetic iron oxide (SPIO) acts as a negative contrast agent in magnetic resonance imaging (MRI), and is widely used in clinical applications, including the diagnosis of hepatic diseases. Hepatocyte-targeted magnetic resonance contrast agents (MRCAs) can provide useful information for evaluating hepatic diseases. We prepared targeted magnetic nanostructured lipid carriers (MNLCs) to enhance the hepatocytes targeting efficiency. Methods In vitro characterizations of MNLCs were determined by transmission electron microscopy (TEM). The cytotoxicity assay of the MNLCs was measured by methyl tetrazolium (MTT) method. The uptaken study was measured by confocal microscopy, flow cytometry and MRI in vitro. The enhanced liver-targeting efficiency of MNLCs was measured by fluorescence imaging and MRI in vivo. Results Gal-NLC-SPIO was prepared successfully. The cytotoxicity assay of the MNLCs demonstrated that the MNLC had relatively low cytotoxicity and high biocompatibility for LO2 cells. More importantly, we confirmed that Gal-NLC-SPIO had greater uptake by LO2 cells than Gal-NLC-SPIO/PEG and free Gal in vitro. A liver distribution study of MNLCs in normal mice demonstrated that the fluorescent signal values to livers of the Gal-NLC-SPIO were significantly stronger than those of NLC-SPIO and Gal-NLC-SPIO/PEG. The liver targeting efficiency of Gal-NLC-SPIO was confirmed both in vitro and in vivo. Conclusions We successfully developed liver-targeting MNLCs, which showed accurate hepatocytes targeting, and thus have the potential to be a new MRI contrast agent to help the diagnosis of liver diseases.