New drug delivery systems are a potential solution for administering drugs to reduce common side effects of traditional methods, such as in cancer therapy. Iron oxide nanoparticles (IONs) can increase the drugs’ biological activity through high binding efficiency and magnetically targeted drug delivery. Understanding the adsorption and release process of a drug to the carrier material plays a significant role in research to generate an applicable and controlled drug delivery system. This contribution focuses on the binding patterns of the peptide lasioglossin III from bee venom on bare IONs. Lasioglossin has a high antimicrobial behavior and due to its cationic properties, it has high binding potential. Considering the influence of pH, the buffer type, the particle concentration, and time, the highest drug loading of 22.7% is achieved in phosphate-buffered saline. Analysis of the desorption conditions revealed temperature and salt concentration sensitivity. The nanoparticles and peptide-ION complexes are analyzed with dynamic light scattering, zeta potential, and infrared spectroscopy. Additionally, cytotoxicity experiments performed on Escherichia coli show higher antimicrobial activity of bound lasioglossin than of the free peptide. Therefore, bare IONs are an interesting platform material for the development of drug-delivery carriers for cationic peptides.

Iron oxide nanoparticles (IONs) are of great interest in nanomedicine for imaging, drug delivery, or for hyperthermia treatment. Although many research groups have focused on the synthesis and application of IONs in nanomedicine, little is known about the influence of the surface properties on the particles' behavior in the human body. This study analyzes the impact of surface coatings (dextran, polyvinyl alcohol, polylactide-co-glycolide) on the nanoparticles’ cytocompatibility, agglomeration, degradation, and the resulting oxidative stress induced by the particle degradation. All particles, including bare IONs (BIONs), are highly cytocompatible (>70%) and show no significant toxicity towards smooth muscle cells. Small-angle X-ray scattering profiles visualize the aggregation behavior of nanoparticles and yield primary particle sizes of around 20 nm for the investigated nanoparticles. A combined experimental setup of dynamic light scattering and phenanthroline assay was used to analyze the long-term agglomeration and degradation profile of IONs in simulated body fluids, allowing fast screening of multiple candidates. All particles degraded in simulated endosomal and lysosomal fluid, confirming the pH-dependent dissolution. The degradation rate decreased with the shrinking size of particles leading to a plateau. The fastest Fe²⁺ release could be measured for the polyvinyl-coated IONs. The analytical setup is ideal for a quick preclinical study of IONs, giving often neglected yet crucial information about the behavior and toxicity of nanoparticles in the human body. Moreover, this study allows for the development and evaluation of novel ferroptosis-inducing agents.

Magnetic nanoparticles (MNPs) are used for magnetophoresis-based separation processes in various biomedical and engineering applications. Essential requirements are the colloidal stability of the MNPs and the ability to be separated even in low magnetic field gradients. Bare iron oxide nanoparticles (BIONs) with a diameter of 9.2 nm are synthesized via coprecipitation, exhibiting a high saturation magnetization of 70.84 Am² kg⁻¹ and no remanence. In our study, zeta potential, dynamic light scattering (DLS), and sedimentation analysis show that the aggregation behavior of BIONs is influenced by pH and viscosity. Small aggregate clusters are formed with either low or high pH values or increased viscosity. Regarding magnetophoresis-based separation, a higher viscosity leads to lower magnetophoretic velocities, similar to how small aggregates do. Additionally, cooperative magnetophoresis, the joint motion of strongly interacting particles, affects the separation of the BIONs, too. Our study emphasizes the effect of pH and viscosity on the physicochemical characteristics of MNPs, resulting in different aggregation behavior. Particularly, for high viscous working media in downstream processing and medicine, respectively, the viscosity should be taken into account, as it will affect particle migration.

Silica-coated iron oxide nanoparticles are of enormous importance in biotechnology, nanomedicine, and catalysis. The study demonstrates the significant influence of the coating thickness on the particle properties. Though slow magnetophoresis, a thinner shell leads to higher surface areas, lower isoelectric points, and higher magnetizations. However, thick layers prevent oxidation and lead to stabilization. The coating thickness influenced the binding of the cationic peptide lasioglossin, with a maximal loading of 0.23 g g⁻¹ for the smallest particles. This knowledge can be used to specifically design particles for usage with a cationic tag system in biotechnology or drug delivery with antimicrobial peptides. Graphical abstract

Carboxymethyl-dextran (CMD)-coated iron oxide nanoparticles (IONs) are of great interest in nanomedicine, especially for applications in drug delivery. To develop a magnetically controlled drug delivery system, many factors must be considered, including the composition, surface properties, size and agglomeration, magnetization, cytocompatibility, and drug activity. This study reveals how the CMD coating thickness can influence these particle properties. ION@CMD are synthesized by co-precipitation. A higher quantity of CMD leads to a thicker coating and a reduced superparamagnetic core size with decreasing magnetization. Above 12.5–25.0 g L⁻¹ of CMD, the particles are colloidally stable. All the particles show hydrodynamic diameters < 100 nm and a good cell viability in contact with smooth muscle cells, fulfilling two of the most critical characteristics of drug delivery systems. New insights into the significant impact of agglomeration on the magnetophoretic behavior are shown. Remarkable drug loadings (62%) with the antimicrobial peptide lasioglossin and an excellent efficiency (82.3%) were obtained by covalent coupling with the EDC/NHS (N-ethyl-N′-(3-(dimethylamino)propyl)carbodiimide/N-hydroxysuccinimide) method in comparison with the adsorption method (24% drug loading, 28% efficiency). The systems showed high antimicrobial activity with a minimal inhibitory concentration of 1.13 µM (adsorption) and 1.70 µM (covalent). This system successfully combines an antimicrobial peptide with a magnetically controllable drug carrier.

Coated iron oxide nanoparticles (IONs) are promising candidates for various applications in nanomedicine, including imaging, magnetic hyperthermia, and drug delivery. The application of IONs in nanomedicine is influenced by factors such as biocompatibility, surface properties, agglomeration, degradation behavior, and thrombogenicity. Therefore, it is essential to investigate the effects of coating material and thickness on the behavior and performance of IONs in the human body. In this study, IONs with a carboxymethyl dextran (CMD) coating and two thicknesses of silica coating (TEOS0.98, and TEOS3.91) were screened and compared to bare iron oxide nanoparticles (BIONs). All three coated particles showed good cytocompatibility (>70%) when tested with smooth muscle cells over three days. To investigate their potential long term behavior inside the human body, the Fe²⁺ release and hydrodynamic diameters of silica-coated and CMD (carboxymethyl dextrane)-coated IONs were analyzed in simulated body fluids for 72 h at 37 °C. The ION@CMD showed moderate agglomeration of around 100 nm in all four simulated fluids and dissolved faster than the silica-coated particles in artificial exosomal fluid and artificial lysosomal fluid. The particles with silica coating agglomerated in all tested simulated media above 1000 nm. Increased thickness of the silica coating led to decreased degradation of particles. Additionally, CMD coating resulted in nanoparticles with the least prothrombotic activity, and the thick silica coating apparently decreased the prothrombotic properties of nanoparticles compared to BIONs and ION@TEOS0.98. For magnetic resonance applications, ION@CMD and ION@TEOS3.91 showed comparatively high relaxation rates R₂ values. In magnetic particle imaging experiments ION@TEOS3.91 yielded the highest normalized signal to noise ratio values and in magnetic hyperthermia studies, ION@CMD and ION@TEOS0.98 showed similar specific loss power. These findings demonstrate the potential of coated IONs in nanomedicine and emphasize the importance of understanding the effect of coating material and thickness on their behavior and performance in the human body.