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Dextran-coated superparamagnetic iron oxide nanoparticles (SPIONDex) of various sizes can be used as contrast agents in magnetic resonance imaging (MRI) of different tissues, e.g., liver or atherosclerotic plaques, after intravenous injection. In previous studies, the blood compatibility and the absence of immunogenicity of SPIONDex was demonstrated. The investigation of the interference of SPIONDex with stimulated immune cell activation is the aim of this study. For this purpose, sterile and endotoxin-free SPIONDex with different hydrodynamic sizes (30 and 80 nm) were investigated for their effect on monocytes, dendritic cells (DC) and lymphocytes in concentrations up to 200 µg/mL, which would be administered for use as an imaging agent. The cells were analyzed using flow cytometry and brightfield microscopy. We found that SPIONDex were hardly taken up by THP-1 monocytes and did not reduce cell viability. In the presence of SPIONDex, the phagocytosis of zymosan and E. coli by THP-1 was dose-dependently reduced. SPIONDex neither induced the maturation of DCs nor interfered with their stimulated maturation. The particles did not induce lymphocyte proliferation or interfere with lymphocyte proliferation after stimulation. Since SPIONDex rapidly distribute via the blood circulation in vivo, high concentrations were only reached locally at the injection site immediately after application and only for a very limited time. Thus, SPIONDex can be considered immune compatible in doses required for use as an MRI contrast agent.

In recent years, many promising nanotechnological approaches to biomedical research have been developed in order to increase implementation of regenerative medicine and tissue engineering in clinical practice. In the meantime, the use of nanomaterials for the regeneration of diseased or injured tissues is considered advantageous in most areas of medicine. In particular, for the treatment of cardiovascular, osteochondral and neurological defects, but also for the recovery of functions of other organs such as kidney, liver, pancreas, bladder, urethra and for wound healing, nanomaterials are increasingly being developed that serve as scaffolds, mimic the extracellular matrix and promote adhesion or differentiation of cells. This review focuses on the latest developments in regenerative medicine, in which iron oxide nanoparticles (IONPs) play a crucial role for tissue engineering and cell therapy. IONPs are not only enabling the use of non-invasive observation methods to monitor the therapy, but can also accelerate and enhance regeneration, either thanks to their inherent magnetic properties or by functionalization with bioactive or therapeutic compounds, such as drugs, enzymes and growth factors. In addition, the presence of magnetic fields can direct IONP-labeled cells specifically to the site of action or induce cell differentiation into a specific cell type through mechanotransduction.

Superparamagnetic iron oxide nanoparticles (SPIONs) feature distinct magnetic properties that make them useful and effective tools for various diagnostic, therapeutic and theranostic applications. In particular, their use in magnetic drug targeting (MDT) promises to be an effective approach for the treatment of various diseases such as cancer. At the cellular level, SPION uptake, along with SPION-mediated toxicity, represents the most important prerequisite for successful application. Thus, the present study determines SPION uptake, toxicity and biocompatibility in human head and neck tumor cell lines of the tongue, pharynx and salivary gland. Using magnetic susceptibility measurements, microscopy, atomic emission spectroscopy, flow cytometry, and plasma coagulation, we analyzed the magnetic properties, cellular uptake and biocompatibility of two different SPION types in the presence and absence of external magnetic fields. Incubation of cells with lauric acid and human serum albumin-coated nanoparticles (SPIONLA-HSA) resulted in substantial particle uptake with low cytotoxicity. In contrast, uptake of lauric acid-coated nanoparticles (SPIONLA) was substantially increased but accompanied by higher toxicity. The presence of an external magnetic field significantly increased cellular uptake of both particles, although cytotoxicity was not significantly increased in any of the cell lines. SPIONs coated with lauric acid and/or human serum albumin show different patterns of uptake and toxicity in response to an external magnetic field. Consequently, the results indicate the potential use of SPIONs as vehicles for MDT in head and neck cancer.

Cytotoxic and cytostatic chemotherapeutics act by attacking rapidly dividing tumor cells, predominantly affecting malignant tissue and to a certain degree preserving healthy cells. Nonetheless, severe side effects are caused as quickly proliferating healthy cells such as hematopoietic precursors and mucous membranes are impaired as well. This limits the administered dose and eventually allows tumor cells to escape treatment. In order to increase intratumoral drug concentration and simultaneously reduce systemic side effects, nanoparticles have come into focus as drug carriers. The functionalization of superparamagnetic iron oxide nanoparticles (SPIONs) with chemotherapeutics such as mitoxantrone (MTO) enables targeted drug transport by using magnetic forces. Here, we investigate SPIONs consisting of individual iron oxide cores of 10 nm in diameter and a total hydrodynamic diameter of 53 ± 0.8 nm as a transporting system for MTO. Comparing the killing efficacy in monolayer cell culture and multicellular tumor spheroids of HT-29 cells, we show that spheroids tolerate considerably higher doses of nanoparticle-loaded MTO. Therefore, dose predictions from conventional monolayer cell cultures are often misleading for in vivo applications. This was true for both soluble and nanoparticle-bound MTO. Using flow chambers mimicking in vivo blood flow, we furthermore demonstrate that SPIONs can magnetically accumulate MTO. We conclude that SPIONs can function as an effective delivery platform to increase local drug concentrations, thereby potentially overcoming chemotherapy resistance of cells.