Abstract

BackgroundSuperparamagnetic iron oxide (SPIO) nanoparticles have been widely used in several biomedical engineering in vivo. Although various surface modifications have been made to these non-biodegradable nanoparticles to make them more biocompatible, their toxic potential still remains a major concern.MethodIn this study, we newly developed unfractionated heparin (UFH)-coated and low molecular weight heparin (LMWH)-coated SPIO nanoparticles through surface modification engineering, which was compared with commercially available dextran-coated SPIO nanoparticles. Their toxicity such as cytotoxicity, single cell gel electrophoresis (SCGE) comet assay, intracellular reactive oxygen species (ROS) content and cellular apoptosis was evaluated to hepatic HepG2 and renal HK-2 cells.ResultsWhen UFH-, LMWH- or dextran-coated SPIO nanoparticles were applied, they did not affect the viability of HepG2 cell. However, HK-2 cells were more sensitive to dextran-coated SPIO nanoparticles than others. In genotoxicity assay using SCGE comet, DNA tail moment values in the groups treated with dextran- and LMWH-coated SPIO nanoparticles significantly increased. However, UFH-coated SPIO nanoparticles was only significantly lowing DNA tail moment value. In addition, UFH-coated SPIO nanoparticles had lower cytotoxicity in HepG2 and HK-2 cells compared to dextran-coated SPIO nanoparticles, especially in terms of apoptosis and intracellular ROS production.ConclusionsCollectively, it is possible that UFH- coated SPIO nanoparticles can be used as alternative negative contrast agents.

Highlights

  • Superparamagnetic iron oxide (SPIO) nanoparticles have been widely used in several biomedical engineering in vivo

  • In genotoxicity assay using single cell gel electrophoresis (SCGE) comet, DNA tail moment values in the groups treated with dextran- and LMWHcoated SPIO nanoparticles significantly increased

  • unfractionated heparin (UFH)-coated SPIO nanoparticles had lower cytotoxicity in HepG2 and HK-2 cells compared to dextran-coated SPIO nanoparticles, especially in terms of apoptosis and intracellular reactive oxygen species (ROS) production

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Summary

Introduction

Superparamagnetic iron oxide (SPIO) nanoparticles have been widely used in several biomedical engineering in vivo. Superparamagnetic iron oxide (SPIO) nanoparticles have been used for various applications, including targeted drug/gene delivery, tissue engineering, and magnetic transfection as a T2 contrast agent [2,3,4]. SPIO nanoparticles decrease signal intensity on T2-weighted and T2*-weighted images (called the ‘blooming effect’); they can generate notable signal loss with high sensitivity (single cell detection) during MRI at concentrations within the picogram range [1, 5]. SPIO nanoparticles vary in size, but they tend to aggregate into large clusters due to their surface-to-volume ratios and dipole-dipole interactions. The fate of SPIO nanoparticles is related to its physicochemical characteristics such as hydrodynamic size and surface charge [7, 8]. The sorts of surfaces coating materials and their functional group can affect in vivo pharmacokinetics and biodistribution of the nanoparticle [9,10,11,12,13]

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