Marija Lovrić

Superparamagnetic Fe3O4 Nanoparticles: Synthesis by Thermal Decomposition of Iron(III) Glucuronate and Application in Magnetic Resonance Imaging.

Monodisperse superparamagnetic Fe3O4 nanoparticles coated with oleic acid were prepared by thermal decomposition of Fe(III) glucuronate. The shape, size, and particle size distribution were controlled by varying the reaction parameters, such as the reaction temperature, concentration of the stabilizer, and type of high-boiling-point solvents. Magnetite particles were characterized by transmission electron microscopy (TEM), as well as electron diffraction (SAED), X-ray diffraction (XRD), dynamic light scattering (DLS), and magnetometer measurements. The particle coating was analyzed by atomic absorption spectroscopy (AAS) and attenuated total reflection (ATR) Fourier transform infrared spectroscopy (FTIR) spectroscopy. To make the Fe3O4 nanoparticles dispersible in water, the particle surface was modified with α-carboxyl-ω-bis(ethane-2,1-diyl)phosphonic acid-terminated poly(3-O-methacryloyl-α-D-glucopyranose) (PMG-P). For future practical biomedical applications, nontoxicity plays a key role, and the PMG-P&Fe3O4 nanoparticles were tested on rat mesenchymal stem cells to determine the particle toxicity and their ability to label the cells. MR relaxometry confirmed that the PMG-P&Fe3O4 nanoparticles had high relaxivity but rather low cellular uptake. Nevertheless, the labeled cells still provided visible contrast enhancement in the magnetic resonance image. In addition, the cell viability was not compromised by the nanoparticles. Therefore, the PMG-P&Fe3O4 nanoparticles have the potential to be used in biomedical applications, especially as contrast agents for magnetic resonance imaging.

Surface coating affects behavior of metallic nanoparticles in a biological environment.

Summary Silver (AgNPs) and maghemite, i.e., superparamagnetic iron oxide nanoparticles (SPIONs) are promising candidates for new medical applications, which implies the need for strict information regarding their physicochemical characteristics and behavior in a biological environment. The currently developed AgNPs and SPIONs encompass a myriad of sizes and surface coatings, which affect NPs properties and may improve their biocompatibility. This study is aimed to evaluate the effects of surface coating on colloidal stability and behavior of AgNPs and SPIONs in modelled biological environments using dynamic and electrophoretic light scattering techniques, as well as transmission electron microscopy to visualize the behavior of the NP. Three dispersion media were investigated: ultrapure water (UW), biological cell culture medium without addition of protein (BM), and BM supplemented with common serum protein (BMP). The obtained results showed that different coating agents on AgNPs and SPIONs produced different stabilities in the same biological media. The combination of negative charge and high adsorption strength of coating agents proved to be important for achieving good stability of metallic NPs in electrolyte-rich fluids. Most importantly, the presence of proteins provided colloidal stabilization to metallic NPs in biological fluids regardless of their chemical composition, surface structure and surface charge. In addition, an assessment of AgNP and SPION behavior in real biological fluids, rat whole blood (WhBl) and blood plasma (BlPl), revealed that the composition of a biological medium is crucial for the colloidal stability and type of metallic NP transformation. Our results highlight the importance of physicochemical characterization and stability evaluation of metallic NPs in a variety of biological systems including as many NP properties as possible.

Does surface coating of metallic nanoparticles modulate their interference with in vitro assays

Screening programs for the evaluation of nanomaterial value and safety rely on in vitro tests. The exceptional physicochemical properties of metallic nanoparticles (NPs), such as large surface area and chemically active surface, may provoke their interference with in vitro methods and analytical techniques used for evaluation of biocompatibility or toxicity of NPs. This study aimed to determine if such interference could be predicted on the basis of the surface characteristics of metallic NPs by investigating the effect of different surface coatings of silver (AgNPs) and maghemite NPs (γ-Fe2O3NPs) on common in vitro assays scoring two of the main cytotoxic endpoints: cell viability and oxidative stress response. We examined optical, adsorptive and chemically reactive types of NP interference with cell viability assays (MTT, MTS, and WST-8) and assays employing fluorescent dyes as markers for production of reactive oxygen species (DCFH-DA and DHE) or glutathione level (MBCl). Each type of tested NPs affected all of the six investigated assays leading to false interpretation of obtained results. The extent and type of interference were dependent on the type and surface coating of NPs as well as on their stability in biological media. The results have shown that interference was concentration-, particle type- and assay type-dependent. This study demonstrated that common in vitro assays, without appropriate cause-and-effect analysis and adaptation or modification, are ineffective in the evaluation of biological effects of metallic NPs due to their interaction with optical readouts and assay components. A comprehensive and feasible experimental setup has been proposed to gain a reproducible and reliable in vitro evaluation as the first step in the health assessment of metallic NPs.