Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) are currently under examination for magnetic particle imaging, which represents a radiation free technology for three-dimensional imaging with high sensitivity, resolution and imaging speed. SPIONs are rapidly taken up by monocytes and other phagocytes which carry them to the site of inflammation. Therefore, the SPION biocompatibility is an essential parameter for a widespread MPI usage. Many improvements are expected from SPION development and its applications for cell visualization, but the impact of MPI optimized dextran coated SPIONs on the cellular characteristics of monocytic cells has been poorly studied up to now. THP-1 monocytes, monocyte-derived macrophages (MDM) as well as peripheral blood monocytes were incubated with MPI-optimized dextran-coated SPIONs of a size between 83.5 and 86 nm. SPION uptake was measured by FITC fluorescence of labeled SPIONs and Prussian blue staining. The activation of monocytes and MDMs was evaluated by CD14, CD11b and CD86 in flow cytometry. The secretion of IL-1β, and IL-10 was analyzed in supernatants. SPIONs were rapidly taken up by monocytes and monocyte-derived macrophages while no decrease in cell viability was observed. Expression patterns of CD11b, CD14, and CD86 were not affected in THP-1 monocytes and MDMs. Monocyte differentiation in macrophages was hindered during SPION uptake. THP-1 monocytes as well as monocyte-derived macrophages showed significantly increased IL-1β and decreased IL-10 secretion by tendency after SPION treatment. Dextran-coated SPIONs showed a low cytotoxicity on monocytes but exert undesirable inflammatory side effects that have to be considered for imaging applications.

Highlights

  • In the past decade, nanoparticles (NPs) found their ways into the clinic as drug delivery systems and imaging contrast agents

  • Aim of the present study was to evaluate the biocompatibility of superparamagnetic Superparamagnetic iron oxide nanoparticles (SPIONs) and monocytes for future magnetic particle imaging to find inflammatory sites

  • The questions of a possible immunoregulatory impact of SPIONs on monocytes was addressed for THP-1 monocytes and primary human monocytes

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Summary

Introduction

Nanoparticles (NPs) found their ways into the clinic as drug delivery systems and imaging contrast agents. There is a great variety of different organic materials such as liposomes, protein based and polymeric particles as well as inorganic metal NPs (Anselmo and Mitragotri 2016). The nanoscale structure as well as the features of superparamagnetism offer a variety of possibilities for diagnosis. Due to their rapid uptake in phagocytes SPIONs are a very useful tool for imaging e.g., liver lesions, lymph node metastasis or atherosclerotic plaques (Anselmo and Mitragotri 2019; Dadfar et al, 2019). In contrast to MRI (magnetic resonance imaging) where similar particles are used, MPI provides a much lower detection threshold and significantly increased sensitivity and spatial resolution (Gleich and Weizenecker 2005; Panagiotopoulos et al, 2015). The MPI technique is ideally suited for applications such as vascular imaging and neuronal imaging as SPIONs are able to pass the blood-brain-barrier as well as cellular and targeted imaging (Weinstein et al, 2010; Panagiotopoulos et al, 2015)

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