Novel magnetic multicore nanoparticles designed for MPI and other biomedical applications: From synthesis to first in vivo studies.

Harald Kratz,Susanne Wagner,Bernd Hamm,Angela Ariza De Schellenberger,Dietmar Eberbeck,Matthias Taupitz,Olaf Kosch,Lutz Trahms,Jörg Schnorr,Raphael Levy

doi:10.1371/journal.pone.0190214

Harald Kratz, Susanne Wagner + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0190214

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Abstract

Synthesis of novel magnetic multicore particles (MCP) in the nano range, involves alkaline precipitation of iron(II) chloride in the presence of atmospheric oxygen. This step yields green rust, which is oxidized to obtain magnetic nanoparticles, which probably consist of a magnetite/maghemite mixed-phase. Final growth and annealing at 90°C in the presence of a large excess of carboxymethyl dextran gives MCP very promising magnetic properties for magnetic particle imaging (MPI), an emerging medical imaging modality, and magnetic resonance imaging (MRI). The magnetic nanoparticles are biocompatible and thus potential candidates for future biomedical applications such as cardiovascular imaging, sentinel lymph node mapping in cancer patients, and stem cell tracking. The new MCP that we introduce here have three times higher magnetic particle spectroscopy performance at lower and middle harmonics and five times higher MPS signal strength at higher harmonics compared with Resovist®. In addition, the new MCP have also an improved in vivo MPI performance compared to Resovist®, and we here report the first in vivo MPI investigation of this new generation of magnetic nanoparticles.

Highlights

Having excellent magnetic properties and good biocompatibility, magnetic nanoparticles (MNP) based on magnetite have many technical and biomedical applications [1,2]
In vitro biocompatibility of multicore particles (MCP) 1 was tested after MNP uptake by mesenchymal stem cells (MSC) and macrophages (RAW 264.7) (S4 Fig and S5 Fig) for their effect on cell proliferation in comparison with unlabeled cells and cells labeled with Resovist1
The innovation of the new synthesis lies in the oxidation of green rust to a probably magnetite/maghemite mixed-phase in conjunction with subsequent annealing and parallel partly reduction at 90 ̊C for several hours

Summary

Introduction

Having excellent magnetic properties and good biocompatibility, magnetic nanoparticles (MNP) based on magnetite have many technical and biomedical applications [1,2]. We compared the uptake of MCP 1 and Resovist1 by nonphagocytic cells (MSC) and phagocytic macrophages (RAW 264.7) using two protocols, with and without transfection agent (TA). In vitro biocompatibility of MCP 1 was tested after MNP uptake by mesenchymal stem cells (MSC) and macrophages (RAW 264.7) (S4 Fig and S5 Fig) for their effect on cell proliferation in comparison with unlabeled cells and cells labeled with Resovist1.

Results

Conclusion