Colloidal stability of magnetic iron oxide nanoparticles (MNP) in physiological environments is crucial for their (bio)medical application. MNP are potential contrast agents for different imaging modalities such as magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). Applied as a hybrid method (MRI/MPI), these are valuable tools for molecular imaging. Continuously synthesized and in-situ stabilized single-core MNP were further modified by albumin coating. Synthesizing and coating of MNP were carried out in aqueous media without using any organic solvent in a simple procedure. The additional steric stabilization with the biocompatible protein, namely bovine serum albumin (BSA), led to potential contrast agents suitable for multimodal (MRI/MPI) imaging. The colloidal stability of BSA-coated MNP was investigated in different sodium chloride concentrations (50 to 150 mM) in short- and long-term incubation (from two hours to one week) using physiochemical characterization techniques such as transmission electron microscopy (TEM) for core size and differential centrifugal sedimentation (DCS) for hydrodynamic size. Magnetic characterization such as magnetic particle spectroscopy (MPS) and nuclear magnetic resonance (NMR) measurements confirmed the successful surface modification as well as exceptional colloidal stability of the relatively large single-core MNP. For comparison, two commercially available MNP systems were investigated, MNP-clusters, the former liver contrast agent (Resovist), and single-core MNP (SHP-30) manufactured by thermal decomposition. The tailored core size, colloidal stability in a physiological environment, and magnetic performance of our MNP indicate their ability to be used as molecular magnetic contrast agents for MPI and MRI.

The optimization of iron oxide nanoparticles as tracers for magnetic particle imaging (MPI) alongside the development of data acquisition equipment and image reconstruction techniques is crucial for the required improvements in image resolution and sensitivity of MPI scanners. We present a large-scale water-based synthesis of multicore superparamagnetic iron oxide nanoparticles stabilized with dextran (MC-SPIONs). We also demonstrate the preparation of single core superparamagnetic iron oxide nanoparticles in organic media, subsequently coated with a poly(ethylene glycol) gallic acid polymer and phase transferred to water (SC-SPIONs). Our aim was to obtain long-term stable particles in aqueous media with high MPI performance. We found that the amplitude of the third harmonic measured by magnetic particle spectroscopy (MPS) at 10 mT is 2.3- and 5.8-fold higher than Resovist for the MC-SPIONs and SC-SPIONs, respectively, revealing excellent MPI potential as compared to other reported MPI tracer particle preparations. We show that the reconstructed MPI images of phantoms using optimized multicore and specifically single-core particles are superior to that of commercially available Resovist, which we utilize as a reference standard, as predicted by MPS.

Magnetic particle imaging (MPI) is a noninvasive tomographic imaging modality for the quantitative visualization of magnetic nanoparticles (MNPs) with high temporal and spatial resolution. The general capability of MPI for cell tracking (e.g., monitoring living cells labeled with MNPs) has successfully been shown. MNPs in cell culture media are often subjected to structural and magnetic changes. In addition to the deteriorating reproducibility, this also complicates the systematic study of the relationship between the MNP properties and their cellular uptake for MPI. Here, we present a method for the preparation of magnetically labeled THP-1 (Tamm–Horsfall Protein-1) monocytes that are used in MPI cell tracking. The method development was performed using two different MPI tracers, which exhibited electrostatic and steric stabilizations, respectively. In the first step, the interaction between the MNPs and cell culture media was investigated and adjusted to ensure high structural and magnetic stability. Furthermore, the influences of the incubation time, MNP concentration used for cellular uptake, and individual preparation steps (e.g., the washing of cells) were systematically investigated. Finally, the success of the developed loading method was demonstrated by the MPI measurements. The presented systematic investigation of the factors that influence the MNP loading of cells will help to develop a reliable and reproducible method for MPI monocyte tracking for the early detection of inflammation in the future.

Micromixer technology is a novel approach to manufacture magnetic single-core iron oxide nanoparticles that offer huge potential for biomedical applications. This platform allows a continuous, scalable, and highly controllable synthesis of magnetic nanoparticles with biocompatible educts via aqueous synthesis route. Since each biomedical application requires specific physical and chemical properties, a comprehensive understanding of the synthesis mechanisms is not only mandatory to control the size and shape of desired nanoparticle systems but, above all, to obtain the envisaged magnetic particle characteristics. The accurate process control of the micromixer technology can be maintained by adjusting two parameters: the synthesis temperature and the residence time. To this end, we performed a systematic variation of these two control parameters synthesizing magnetic nanoparticle systems, which were analyzed afterward by structural (transmission electron microscopy and differential sedimentation centrifugation) and, especially, magnetic characterization methods (magnetic particle spectroscopy and AC susceptibility). Furthermore, we investigated the reproducibility of the microtechnological nanoparticle manufacturing process compared to batch preparation. Our characterization demonstrated the high magnetic quality of single-core iron oxide nanoparticles with core diameters in the range of 20 nm to 40 nm synthesized by micromixer technology. Moreover, we demonstrated the high capability of a newly developed benchtop magnetic particle spectroscopy device that directly monitored the magnetic properties of the magnetic nanoparticles with the highest sensitivity and millisecond temporal resolution during continuous micromixer synthesis.

The quantification of magnetic iron oxide nanoparticles in biological systems (cells, tissues and organs) is of vital importance in the development of novel biomedical applications such as magnetofection, drug targeting or hyperthermia. Among several techniques established to detect iron in tissue, the recently developed technique of magnetic particle spectroscopy (MPS) provides signals that are specific for magnetic nanoparticles. MPS utilizes the non-linear response of an MNP sample to a strong sinusoidal excitation field of up to 25 mT amplitude and 25 kHz. We demonstrate the feasibility of this technique to quantify nanoparticle uptake in cells using a commercial magnetic particle spectrometer (Bruker BioSpin).