Polymer-coated superparamagnetic iron oxide nanoparticles as T2 contrast agent for MRI and their uptake in liver.

AIM: To study the efficiency of multifunctional polymer-based superparamagnetic iron oxide nanoparticles (bioferrofluids) as a T2 magnetic resonance contrast agent and their uptake and toxicity in liver. MATERIALS & METHODS: Mice were intravenously injected with bioferrofluids and Endorem®. The magnetic resonance efficiency, uptake and in vivo toxicity were investigated by means of magnetic resonance imaging (MRI) and histological techniques. RESULTS: Bioferrofluids are a good T2 contrast agent with a higher r2/r1 ratio than Endorem. Bioferrofluids have a shorter blood circulation time and persist in liver for longer time period compared with Endorem. Both bioferrofluids and Endorem do not generate any noticeable histological lesions in liver over a period of 60 days post-injection. CONCLUSION: Our bioferrofluids are powerful diagnostic tool without any observed toxicity over a period of 60 days post-injection.

Cell compatibility of a maghemite/polymer biomedical nanoplatform.

We are reporting the cytocompatibility and cellular fate of an iron oxide/polymer nanoplatform (IONP) in its most basic formulation, using both mesenchymal (vascular smooth muscle cells, VSMC), and epithelial (opossum kidney, OK) cells. The cytotoxicity and cell internalization of the nanoplatform has been evaluated in relation to time of exposure and concentration of different components. A series of samples with different iron oxide nanoparticle, sizes, hydrodynamic sizes and iron/polymer ratio have been examined. In all cases cytotoxicity is low, and it is mostly determined by the internalization rate, being higher in VSMC than in OK cells. The mean lethal dose has a very narrow threshold, and necrosis is the only cell death type. IONP uptake shows little incidence on oxidative stress, and inflammasome activation is only observed with the smaller IONP at high concentration. The internalization rate in VSMC is determined by the polymer concentration exclusively. In OK cells, internalization rate seems to increase with decreasing hydrodynamic size. Internalization occurs through clathrin-dependent endocytosis, as it is prevented by potassium depletion and chlorpromazine. IONP are directed and accumulated in lysosomes. Under IONP overload, lysosomal dysfunction would cause cell death using concentrations that are hardly achieved in vivo.

Hemostasis disorders caused by polymer coated iron oxide nanoparticles.

BACKGROUND: Superparamagnetic iron oxide nanoparticles (SPIONs) are inorganic nanomaterials gaining strong clinical interest due to their increasing number of biological and medical applications. The stabilization of SPIONs in a biocompatible stable suspension (bioferrofluid) is generally achieved by an adequate polymeric coating. As many applications using these materials are intended for clinical use through intravenous injection, it is of outmost importance to evaluate their hemostatic behaviour. OBJECTIVES: The aim of this work is to evaluate the hemocompatibility of selected polymer coated bioferrofluids and of their separated components by observing the effects of the bioferrofluid on: the coagulation process--by measuring the prothrombin time (PT) and activated partial thromboplastin time (aPTT)--, the complete blood count (CBC)--Erythrocytes, Leucocytes, Platelets, Hemoglobin and hematocrit--and the hemolysis. METHODS: A SPIONs/bioferrofluid model consisting of a magnetic core of iron oxide nanoparticles embedded within poly(4-vinyl pyridine) (P4VP) and all coated with polyethylene glycol (PEG) has been selected. RESULTS AND CONCLUSIONS: By increasing the concentration of the bioferrofluids an inhibitory effect on the intrinsic pathway of blood coagulation is observed, as indicated by significant increase in aPTT in vitro while PT values stay normal. The effect of the coating components on the inhibition of blood coagulation process shows that PEG has no effect on the process while the P4VP-g-PEG copolymer coating has a strong anticoagulant effect indicating that P4VP is at the origin of such effects. The studied bioferrofluids have no effect on the CBC neither they show in vitro hemolytic effect on blood.

Magnetic and relaxation properties of multifunctional polymer-based nanostructured bioferrofluids as MRI contrast agents.

A series of maghemite/polymer composite ferrofluids with variable magnetic core size, which show a good efficiency as MRI contrast agents, are presented. These ferrofluids are biocompatible and can be proposed as possible platforms for multifunctional biomedical applications, as they contain anchoring groups for biofunctionalization, can incorporate fluorescent dyes, and have shown low cellular toxicity. The magnetic properties of the ferrofluids have been determined by means of magnetization and ac susceptibility measurements as a function of temperature and frequency. The NMR dispersion profiles show that the low frequency behavior of the longitudinal relaxivity r(1) is well described by the heuristic model of (1)H nuclear relaxation induced by superparamagnetic nanoparticles proposed by Roch and co-workers. The contrast efficiency parameter, i.e., the nuclear transverse relaxivity r(2), for samples with d > 10 nm assumes values comparable with or better than the ones of commercial samples, the best results obtained in particles with the biggest magnetic core, d = 15 nm. The contrast efficiency results are confirmed by in vitro MRI experiments at ν = 8.5 MHz, thus allowing us to propose a set of optimal microstructural parameters for multifunctional ferrofluids to be used in MRI medical diagnosis.