N-Acetylcysteine-Loaded Magnetic Nanoparticles for Magnetic Resonance Imaging.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by the rapid onset of lung inflammation Therefore, monitoring the spatial distribution of the drug directly administered to heterogeneously damaged lungs is desirable. In this work, we focus on optimizing the drug N-acetylcysteine (NAC) adsorption on poly-l-lysine-modified magnetic nanoparticles (PLLMNPs) to monitor the drug spatial distribution in the lungs using magnetic resonance imaging (MRI) techniques. The physicochemical characterizations of the samples were conducted in terms of morphology, particle size distributions, surface charge, and magnetic properties followed by the thermogravimetric quantification of NAC coating and cytotoxicity experiments. The sample with the theoretical NAC loading concentration of 0.25 mg/mL was selected as an optimum due to the hydrodynamic nanoparticle size of 154 nm, the surface charge of +32 mV, good stability, and no cytotoxicity. Finally, MRI relaxometry confirmed the suitability of the sample to study the spatial distribution of the drug in vivo using MRI protocols. We showed the prevailing transverse relaxation with high transverse relaxivity values and a high r2(*)/r1 ratio, causing visible hypointensity in the final MRI signal. Furthermore, NAC adsorption significantly affects the relaxation properties of PLLMNPs, which can help monitor drug release in vitro/in vivo.

Development of Positively Charged Poly-L-Lysine Magnetic Nanoparticles as Potential MRI Contrast Agent.

A colloidal solution of magnetic nanoparticles (MNPs) modified with biocompatible positively charged poly-L-lysine (PLL) with an oleate (OL) layer employed as an initial coating was produced as a potential MRI contrast agent. The effect of various PLL/MNPs' mass ratios on the samples' hydrodynamic diameter, zeta potential, and isoelectric point (IEP) was studied by the dynamic light-scattering method. The optimal mass ratio for MNPs' surface coating was 0.5 (sample PLL0.5-OL-MNPs). The average hydrodynamic particle size in the sample of PLL0.5-OL-MNPs was 124.4 ± 1.4 nm, and in the PLL-unmodified nanoparticles, it was 60.9 ± 0.2 nm, indicating that the OL-MNPs' surface became covered by PLL. Next, the typical characteristics of the superparamagnetic behavior were observed in all samples. In addition, the decrease in saturation magnetizations from 66.9 Am2/kg for MNPs to 35.9 and 31.6 Am2/kg for sample OL-MNPs and PLL0.5-OL-MNPs also confirmed successful PLL adsorption. Moreover, we show that both OL-MNPs and PLL0.5-OL-MNPs exhibit excellent MRI relaxivity properties and a very high r2(*)/r1 ratio, which is very desirable in biomedical applications with required MRI contrast enhancement. The PLL coating itself appears to be the crucial factor in enhancing the relaxivity of MNPs in MRI relaxometry.

Design and preparation of proline, tryptophan and poly-l-lysine functionalized magnetic nanoparticles and their radiolabeling with 131I and 177Lu for potential theranostic use.

Surface modification of magnetic nanoparticles with poly-l-lysine, proline, and tryptophan was used to design potential theranostic agents for the application in cancer diagnosis and radionuclide-hyperthermia therapy. Characterization of bare and functionalized magnetic nanoparticles was performed in detail. The transparency of the examined magnetic nanoparticles was measured in the non-alternating magnetic field for a complete and better understanding of hyperthermia. For the first time amino acid-functionalized magnetic nanoparticles were labeled with theranostic radionuclides 131I and 177Lu. The specific absorption rate (SAR) procured for poly-l-lysine functionalized magnetic nanoparticles (SAR values of 99.7 W/g at H0 = 15.9 kA/m and resonant frequency of 252 kHz) demonstrated their possible application in magnetic hyperthermia. Poly-l-lysine functionalized magnetic nanoparticles labeled with 177Lu showed the highest radiochemical purity (>99.00 %) and in vitro stability in saline and serum (>98.00 % up to 96 h). The in vivo analysis performed after their intravenous administration in healthy Wistar rats presented good in vivo stability for several days. Encouraging results as well as magnetic and radiochemical properties of 177Lu-PLL-MNPs (80 °C) justify their further testing toward the potential use as theranostic agents for diagnostic and combined radionuclide-hyperthermia therapeutic applications.

Targeting of carbonic anhydrase IX-positive cancer cells by glycine-coated superparamagnetic nanoparticles.

Antibody-modified magnetic nanoparticles were prepared to study their cellular uptake in 3D multicellular spheroidal cell cultures. For this purpose, carbonic anhydrase IX specific monoclonal antibody VII/20 was selected to conjugate on the surface of positively charged glycine coated magnetic nanoparticles in a form of a stable magnetic fluid. In this work, glycine-functionalized magnetic nanoparticles were characterized by different methods. X-ray photoelectron analysis confirmed the binding of glycine to the magnetic nanoparticles, and quantification of the glycine coating on the surface of the magnetic nanoparticles was conducted by thermogravimetric analysis. The optimal weight ratio of glycine to magnetic nanoparticles was determined to be 5 showing good colloid stability due to the high surface charge density of protonated glycine coating shown by the great zeta potential (⁓40 mV). The antibody conjugation to the functionalized magnetic nanoparticles was performed at an antibody to magnetic nanoparticles weight ratio equal to 0.5. Applications of antibody-modified magnetic nanoparticles in cancer therapy rely on their ability to specifically target cancer tissues and enter the tumour intracellular space. Here, we show that antibody coupled nanoparticle internalization was triggered by selective binding to tumour cells expressing hypoxic marker carbonic anhydrase IX. Moreover, our results confirmed specific penetration of conjugated nanoparticles into the tumour cell spheroids.

Influence of Dextran Molecular Weight on the Physical Properties of Magnetic Nanoparticles for Hyperthermia and MRI Applications.

Dextran-coated magnetic nanoparticles are promising biocompatible agents in various biomedical applications, including hyperthermia and magnetic resonance imaging (MRI). However, the influence of dextran molecular weight on the physical properties of dextran-coated magnetic nanoparticles has not been described sufficiently. We synthesise magnetite nanoparticles with a dextran coating using a co-precipitation method and study their physical properties as a function of dextran molecular weight. Several different methods are used to determine the size distribution of the particles, including microscopy, dynamic light scattering, differential centrifugal sedimentation and magnetic measurements. The size of the dextran-coated particles increases with increasing dextran molecular weight. We find that the molecular weight of dextran has a significant effect on the particle size, efficiency, magnetic properties and specific absorption rate. Magnetic hyperthermia measurements show that heating is faster for dextran-coated particles with higher molecular weight. The different molecular weights of the coating also significantly affected its MRI relaxation properties, especially the transversal relaxivity r2. Linear regression analysis reveals a statistically significant dependence of r2 on the differential centrifugal sedimentation diameter. This allows the targeted preparation of dextran-coated magnetic nanoparticles with the desired MRI properties. These results will aid the development of functionalised magnetic nanoparticles for hyperthermia and MRI applications.

Amino Acid Functionalized Superparamagnetic Nanoparticles Inhibit Lysozyme Amyloid Fibrillization.

Nanoparticles have great potential to be used in various biomedical applications, including therapy or diagnosis of amyloid-related diseases. The physical and chemical properties of iron oxide superparamagnetic nanoparticles (MNPs) functionalized with different amino acids (AAs), namely, with lysine (Lys), glycine (Gly), or tryptophan (Trp), have been characterized. The cytotoxicity of nanoparticles and their effect on amyloid fibrillization of lysozymes in vitro was also verified. The AA-MNPs under study are nontoxic to human SHSY5Y neuroblastoma cells. Moreover, the AA-MNPs were able to significantly inhibit lysozyme amyloid fibrillization and destroy amyloid fibrils. Kinetic studies revealed that the presence of AA-MNPs affected lysozyme fibrillization, namely, the lag phase and steady-state phase of the growth curves. The most effective activities were observed for Trp-MNPs, which revealed the importance of aromatic rings in the structure of AAs used as coating agents. The obtained results indicate the possible application of these AA-MNPs in the treatment of amyloid diseases associated with lysozyme or other amyloidogenic proteins.

Tuning the phase transition temperature of ferronematics with a magnetic field.

The influence of magnetic field on the isotropic-to-nematic phase transition temperature is investigated in neat bent-core and calamitic liquid crystals, in their mixture, and in samples doped with spherical magnetic nanoparticles for two different orientations of the magnetic field. A magnetic-field-induced negative or positive shift of the transition temperature was detected depending on the magnetic field orientation with respect to the initial orientation of the nematic phase, and on the type of liquid crystal matrix.