3-Aminopropylsilane-modified iron oxide nanoparticles for contrast-enhanced magnetic resonance imaging of liver lesions induced by Opisthorchis felineus

Alexander M Demin,1,* Alexandra G Pershina,2,3,* Vladimir V Ivanov,2 Kseniya V Nevskaya,2 Oleg B Shevelev,4 Artyom S Minin,5 Iliya V Byzov,5 Alexey E Sazonov,2 Victor P Krasnov,1 Ludmila M Ogorodova2 1Postovsky Institute of Organic Synthesis of RAS (Ural Branch), Yekaterinburg, 2Siberian State Medical University, 3Russian National Research Tomsk Polytechnic University, Tomsk, 4Institute of Cytology and Genetics SB RAS, Novosibirsk, 5Miheev Institute of Metal Physics of RAS (Ural Branch), Yekaterinburg, Russia *These authors contributed equally to this work Purpose: Liver fluke causes severe liver damage in an infected human. However, the infection often remains neglected due to the lack of pathognomonic signs. Nanoparticle-enhanced magnetic resonance imaging (MRI) offers a promising technique for detecting liver lesions induced by parasites.Materials and methods: Surface modification of iron oxide nanoparticles produced by coprecipitation from a solution of Fe3+ and Fe2+ salts using 3-aminopropylsilane (APS) was carried out. The APS-modified nanoparticles were characterized by transmission electron microscopy, fourier transform infrared spectroscopy, and thermogravimetric analysis . Magnetic resonance properties of MNPs were investigated in vitro and in vivo.Results: The amount of APS grafted on the surface of nanoparticles (0.60±0.06 mmol g-1) was calculated based on elemental analysis and infrared spectroscopy data. According to transmission electron microscopy data, there were no essential changes in the structure of nanoparticles during the modification. The APS-modified nanoparticles exhibit high magnetic properties; the calculated relaxivity r2 was 271 mmol-1 s-1. To obtain suspension with optimal hydrodynamic characteristics, amino groups on the surface of nanoparticles were converted into an ionic form with HCl. Cellular uptake of modified nanoparticles by rat hepatoma cells and human monocytes in vitro was 74.1±4.5 and 10.0±3.7 pg [Fe] per cell, respectively. Low cytotoxicity of the nanoparticles was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Annexin V/7-aminoactinomycin D flow cytometry assays. For the first time, magnetic nanoparticles were applied for contrast-enhanced MRI of liver lesions induced by Opisthorchis felineus.Conclusion: The synthesized APS-modified iron oxide nanoparticles showed high efficiency as an MRI contrast agent for the evaluation of opisthorchiasis-related liver damage. Keywords: magnetic nanoparticles, alkoxysilane, magnetic resonance imaging, liver fluk