Aliskiren, a renin inhibitor, has been shown to have cardioprotective and blood pressure (BP) lowering effects. We aimed to determine the effects of nanoparticle-loaded aliskiren on BP, nitric oxide synthase activity (NOS) and structural alterations of the heart and aorta developed due to spontaneous hypertension in rats. Twelve week-old male spontaneously hypertensive rats (SHR) were divided into the untreated group, group treated with powdered or nanoparticle-loaded aliskiren (25 mg/kg/day) and group treated with nanoparticles only for 3 weeks by gavage. BP was measured by tail-cuff plethysmography. NOS activity, eNOS and nNOS protein expressions, and collagen content were determined in both the heart and aorta. Vasoactivity of the mesenteric artery and wall thickness, inner diameter, and cross-sectional area (CSA) of the aorta were analyzed. After 3 weeks, BP was lower in both powdered and nanoparticle-loaded aliskiren groups with a more pronounced effect in the latter case. Only nanoparticle-loaded aliskiren increased the expression of nNOS along with increased NOS activity in the heart (by 30%). Moreover, nanoparticle-loaded aliskiren decreased vasoconstriction of the mesenteric artery and collagen content (by 11%), and CSA (by 25%) in the aorta compared to the powdered aliskiren group. In conclusion, nanoparticle-loaded aliskiren represents a promising drug with antihypertensive and cardioprotective effects.
In this study, we analysed the physico-chemical properties of positively charged magnetic fluids consisting of magnetic nanoparticles (MNPs) functionalised by different amino acids (AAs): glycine (Gly), lysine (Lys) and tryptophan (Trp), and the influence of AA–MNP complexes on the MRI relaxivity. We found that the AA coating affects the size of dispersed particles and isoelectric point, as well as the zeta potential of AA–MNPs differently, depending on the AA selected. Moreover, we showed that a change in hydrodynamic diameter results in a change to the relaxivity of AA–MNP complexes. On the one hand, we observed a decrease in the relaxivity values, r1 and r2, with an increase in hydrodynamic diameter (the relaxivity of r1 and r2 were comparable with commercially available contrast agents); on the other hand, we observed an increase in r2* value with an increase in hydrodynamic size. These findings provide an interesting preliminary look at the impact of AA coating on the relaxivity properties of AA–MNP complexes, with a specific application in molecular contrast imaging originating from magnetic nanoparticles and magnetic resonance techniques.
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.
Diagnosis of oncological diseases remains at the forefront of current medical research. Carbonic Anhydrase IX (CA IX) is a cell surface hypoxia-inducible enzyme functionally involved in adaptation to acidosis that is expressed in aggressive tumors; hence, it can be used as a tumor biomarker. Herein, we propose a nanoscale graphene oxide (GO) platform functionalized with magnetic nanoparticles and a monoclonal antibody specific to the CA IX marker. The GO platforms were prepared by a modified Hummers and Offeman method from exfoliated graphite after several centrifugation and ultrasonication cycles. The magnetic nanoparticles were prepared by a chemical precipitation method and subsequently modified. Basic characterization of GO, such as the degree of oxidation, nanoparticle size and exfoliation, were determined by physical and chemical analysis, including X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), energy dispersive X-ray analysis (EDX), and atomic force microscopy (AFM). In addition, the size and properties of the poly-L-lysine-modified magnetic nanoparticles were characterized. The antibody specific to CA IX was linked via an amidic bond to the poly-L-lysine modified magnetic nanoparticles, which were conjugated to GO platform again via an amidic bond. The prepared GO-based platform with magnetic nanoparticles combined with a biosensing antibody element was used for a hypoxic cancer cell targeting study based on immunofluorescence.
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.