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| In vitro experimental study of asialoglycoprotein receptor-mediated superparamagnetic nanoparticles as a novel hepatocyte-targeted magnetic resonance contrast agent |
| LIU Guan-yu1, LIU Yi2 |
| 1. Department of Medical Imaging, Liaoning Cancer Hospital & Institute, Shenyang 110042, China;
2. Department of Medical Imaging, the First Hospital of China Medical University, Shenyang 110001, China |
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Abstract Objective: To explore the specificity of novel hepatocyte-targeted magnetic resonance contrast agent(Fe-HSA-LA) mediated by asialoglycoprotein receptor(ASGPR) for BRL 3A cells and the feasibility of MR. Methods: After synthesizing the asialoglycoprotein receptor-mediated hepatocyte-targeted magnetic resonance contrast agents(Fe-HSA-LA). It’s characterization was observed by transmission electron microscope(TEM), and the T2 relaxation rate was measured by MR. The cytotoxicity of Fe-HSA-LA was measured by CCK-8 method. BRL 3A cells and Colon26 cells were incubated with Fe-HSA-LA and PEG-USPIO at concentrations of 10 μg Fe/mL and 50 μg Fe/mL, respectively, and stained with Prussian blue. MR T2 weighted imaging and T2 map imaging were performed on the cell suspension, and the bound iron content of each group of labeled cells was determined by atomic absorption spectroscopy(AAS). Results: The Z-average hydrated particle sizes of Fe-HSA-LA and PEG-USPIO were (53.38±17.07) nm and (16.57±4.18) nm, the Zeta potentials were (-23.3±9.10) mV and (2.57±0.83) mV, and the T2 relaxation rates were 168.4 mM-1s-1 and 416.3 mM-1s-1, respectively. The cytotoxicity experiment showed that the cell viability of BRL 3A cells was over 95% when the concentration of Fe-HSA-LA was ≤50 μg Fe/mL. The MR T2 and the AAS results showed that when the iron incubation concentration was equal to or greater than 3.125 μg Fe/mL, the signal intensity of the Fe-HSA-LA labeled BRL 3A cells decreased obviously, and the iron content of the labeled cells was the highest(P<0.05). There was a good correlation between the MR R2 value and the intracellular iron content. Conclusion: Fe-HSA-LA nanoparticles had good targeting specificity for BRL 3A cells and could be monitored with 3.0T MR．
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Received: 09 October 2019
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| [1]高媛悦，刘爱赟，沈佳佳，等. 去唾液酸糖蛋白受体介导的肝肿瘤靶向载药系统研究进展[J]. 中国药科大学学报，2016，47（5）：537-542.
[2]Massarelli I, Chiellini F, Chiellini E, et al. Three-dimensional models of the oligomeric human asialoglycoprotein receptor(ASGP-R)[J]. Int J Mol Sci, 2010, 11(10): 3867-3884.
[3]Sanhueza CA, Baksh MM, Thuma B, et al. Efficient Liver Targeting by Polyvalent Display of a Compact Ligand for the Asialoglycoprotein Receptor[J]. J Am Chem Soc, 2017, 139(9): 3528-3536.
[4]Kang JH, Toita R, Murata M. Liver cell-targeted delivery of therapeutic molecules[J]. Crit Rev Biotechnol, 2016, 36(1): 132-143.
[5]Kaibori M, Ha-Kawa SK, Maehara M, et al. Usefulness of Tc-99m-GSA scintigraphy for liver surgery[J]. Ann Nucl Med, 2011, 25(9): 593-602.
[6]Wáng YX, Idée JM. A comprehensive literatures update of clinical researches of superparamagnetic resonance iron oxide nanoparticles for magnetic resonance imaging[J]. Quant Imaging Med Surg, 2017, 7(1): 88-122.
[7]Song L, Zang F, Song M, et al. Effective PEGylation of Fe3O4 Nanomicelles for In Vivo MR Imaging[J]. J Nanosci Nanotechnol, 2015, 15(6): 4111-4118.
[8]Mkhwanazi NK, de Koning CB, van Otterlo WA, et al. PEGylation potentiates hepatoma cell targeted liposome-mediated in vitro gene delivery via the asialoglycoprotein receptor[J]. Z Naturforsch C, 2017, 72(7-8): 293-301.
[9]Li SD, Huang L. Nanoparticles evading the reticuloendothelial system: role of the supported bilayer[J]. Biochim Biophys Acta, 2009, 1788(10): 2259-2266.
[10]Rimac H, Debeljak Z, Bojic M, et al. Displacement of Drugs from Human Serum Albumin: From Molecular Interactions to Clinical Significance[J]. Curr Med Chem, 2017, 24(18): 1930-1947.
[11]Tong S, Hou S, Zheng Z, et al. Coating optimization of superparamagnetic iron oxide nanoparticles for high T2 relaxivity[J]. Nano Lett, 2010, 10(11): 4607-4613.
[12]Chen L, McCrate JM, Lee JC, et al. The role of surface charge on the uptake and biocompatibility of hydroxyapatite nanoparticles with osteoblast cells[J]. Nanotechnology, 2011, 22(10): 105708.
[13]Hajesmaeelzadeh F, Shanehsazzadeh S, Gruttner C, et al. Effect of coating thickness of iron oxide nanoparticles on their relaxivity in the MRI[J]. Iran J Basic Med Sci, 2016, 19(2): 166-171.
[14]Huang J, Bu L, Xie J, et al. Effects of nanoparticle size on cellular uptake and liver MRI with polyvinylpyrrolidone-coated iron oxide nanoparticles[J]. ACS Nano, 2010, 4(12): 7151-7160.
[15]Wicki A, Witzigmann D, Balasubramanian V, et al. Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications[J]. J Control Release, 2015, 200: 138-157. |
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