Marcus Stapf

Superparamagnetic iron oxide nanoparticles (SPIONs) are frequently used for drug targeting, hyperthermia and other biomedical purposes. Recently, we have reported the synthesis of lauric acid-/albumin-coated iron oxide nanoparticles SEON^LA-BSA, which were synthesized using excess albumin. For optimization of magnetic treatment applications, SPION suspensions need to be purified of excess surfactant and concentrated. Conventional methods for the purification and concentration of such ferrofluids often involve high shear stress and low purification rates for macromolecules, like albumin. In this work, removal of albumin by low shear stress tangential ultrafiltration and its influence on SEON^LA-BSA particles was studied. Hydrodynamic size, surface properties and, consequently, colloidal stability of the nanoparticles remained unchanged by filtration or concentration up to four-fold (v/v). Thereby, the saturation magnetization of the suspension can be increased from 446.5 A/m up to 1667.9 A/m. In vitro analysis revealed that cellular uptake of SEON^LA-BSA changed only marginally. The specific absorption rate (SAR) was not greatly affected by concentration. In contrast, the maximum temperature T_max in magnetic hyperthermia is greatly enhanced from 44.4 °C up to 64.9 °C by the concentration of the particles up to 16.9 mg/mL total iron. Taken together, tangential ultrafiltration is feasible for purifying and concentrating complex hybrid coated SPION suspensions without negatively influencing specific particle characteristics. This enhances their potential for magnetic treatment.

Magnetically induced heating of magnetic nanoparticles (MNP) in an alternating magnetic field (AMF) is a promising minimally invasive tool for localized tumor treatment by sensitizing or killing tumor cells with the help of thermal stress. Therefore, the selection of MNP exhibiting a sufficient heating capacity (specific absorption rate, SAR) to achieve satisfactory temperatures in vivo is necessary. Up to now, the SAR of MNP is mainly determined using ferrofluidic suspensions and may distinctly differ from the SAR in vivo due to immobilization of MNP in tissues and cells. The aim of our investigations was to study the correlation between the SAR and the degree of MNP immobilization in dependence of their physicochemical features. In this study, the included MNP exhibited varying physicochemical properties and were either made up of single cores or multicores. Whereas the single core MNP exhibited a core size of approximately 15 nm, the multicore MNP consisted of multiple smaller single cores (5 to 15 nm) with 65 to 175 nm diameter in total. Furthermore, different MNP coatings, including dimercaptosuccinic acid (DMSA), polyacrylic acid (PAA), polyethylenglycol (PEG), and starch, wereinvestigated. SAR values were determined after the suspension of MNP in water. MNP immobilization in tissues was simulated with 1% agarose gels and 10% polyvinyl alcohol (PVA) hydrogels. The highest SAR values were observed in ferrofluidic suspensions, whereas a strong reduction of the SAR after the immobilization of MNP with PVA was found. Generally, PVA embedment led to a higher immobilization of MNP compared to immobilization in agarose gels. The investigated single core MNP exhibited higher SAR values than the multicore MNP of the same core size within the used magnetic field parameters. Multicore MNP manufactured via different synthesis routes (fluidMAG-D, fluidMAG/12-D) showed different SAR although they exhibited comparable core and hydrodynamic sizes. Additionally, no correlation between ζ-potential and SAR values after immobilization was observed. Our data show that immobilization of MNP, independent of their physicochemical properties, can distinctly affect their SAR. Similar processes are supposed to take place in vivo, particularly when MNP are immobilized in cells and tissues. This aspect should be adequately considered when determining the SAR of MNP for magnetic hyperthermia.