Xiuliang Zhu1, Xueying Deng2, Chenying Lu1, Ying Chen1, Liyong Jie1, Qian Zhang1, Wei Li3, Zuhua Wang4, Yongzhong Du3, Risheng Yu1. 1. Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China. 2. Department of Radiology, Zhejiang Cancer Hospital, Hangzhou 310022, China. 3. Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. 4. College of Pharmaceutical Sciences, Guiyang College of Traditional Chinese Medicine, Guiyang 550002, China.
Abstract
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.
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.
Entities:
Keywords:
Superparamagnetic iron oxide (SPIO); liver-targeted; magnetic resonance imaging (MRI); solid lipid nanoparticle galactose (SLN galactose)
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