In Vivo Evaluation of DMSA-Coated Magnetic Nanoparticle Toxicity and Biodistribution in Rats: A Long-Term Follow-Up.

This work presents a long-term follow-up (300 days) of rats after a single intravenous injection of DMSA-coated magnetite nanoparticles (DMSA-MNP). The animals were systematically evaluated by hematological, biochemical, and ultrasound examinations, monitoring the same animal over time. In addition, oxidative stress evaluation, DMSA-MNP biodistribution, computerized tomography for ex vivo organs, and histopathology analysis were performed at the end of the experiment period. Overall, DMSA-MNP administration did not cause serious damage to the rats' health over the course of 300 days post-administration. All animals presented hematological parameters within the normal limits, and no alterations on serum creatinine, urea, ALT, and AST were related to DMSA-MNP administration. Liver and spleen showed no important alterations in any of the examinations. The kidneys of treated animals displayed intermittent pelvis dilation at ultrasound analysis, but without damage to the organ parenchyma after 300 days. The lungs of treated animals presented a light interalveolar septal thickening, but the animals did not present any clinical respiratory symptom. Nanoparticles were not detected in the vital organs of treated animals 300 days after administration. This work represents the first assessment of the long-term effects of DMSA-MNP and goes a step further on the safety of its use for biomedical applications.

Synergistic Antitumor Efficacy of Magnetohyperthermia and Poly(lactic-co-glycolic acid)-Encapsulated Selol in Ehrlich Breast Adenocarcinoma Treatment in Elderly Swiss Mice.

Nanobiotechnology strategies for cancer treatments are currently being tested with increasing interest, except in elderly groups. It is well established that breast cancer incidence increases with age and that traditional therapies usually generate severe adverse effects, especially for elderly groups. To investigate if the benefits of nanotechnology could be extended to treating cancer in this group, citrate-coated maghemite nanoparticles (NpCit) were used for magnetohyperthermia (MHT) in combination with the administration of PLGA-Selol nanocapsule (NcSel), a formulation with antioxidant and antitumor activity. The combined therapies significantly inhibited breast Ehrlich tumor growth and prevented metastases to the lymph nodes, liver and lungs until 45 days after tumor induction, a better result than the group undergoing conventional drug treatment. The levels of TNF-α, associated with poor prognosis in Ehrlich tumor, were also normalized. Therefore, the results evidenced the potential use of these therapies for future clinical trials in elderly breast cancer patients.

Phonophoretic application of a glucosamine and chondroitin nanoemulsion for treatment of knee chondropathies.

Aim: This study was performed to assess the effect of the phonophoretic application of a nanoemulsion incorporating glucosamine and chondroitin sulfate (NANO-CG) associated with kinesiotherapy on the reduction of pain and stiffness in knee chondropathy. Materials & methods: NANO-CG was tested in vitro and in vivo prior to being applied in a randomized and controlled clinical trial. Results: Cell viability and hen's egg test-chorionallantonic membrane tests indicated the NANO-CG is safe for topical application. Permeation tests showed NANO-CG enhances drug permeation through the skin. There was no statistical significance between treated groups in this preliminary study, however, pain reduction and complete recovery of articular cartilage were observed in some patients treated with NANO-CG. Conclusion: We demonstrate that NANO-CG may be a promising candidate for the therapy of knee chondropathy.

Highly Magnetizable Crosslinked Chloromethylated Polystyrene-Based Nanocomposite Beads for Selective Molecular Separation of 4-Aminobenzoic Acid.

In this work, we describe the preparation and characterization of highly magnetizable chloromethylated polystyrene-based nanocomposite beads. For synthesis optimization, acid-resistant core-shelled maghemite (γ-Fe2O3) nanoparticles are coated with sodium oleate and directly incorporated into the organic medium during a suspension polymerization process. A crosslinking agent, ethylene glycol dimethacrylate, is used for copolymerization with 4-vinylbenzyl chloride to increase the resistance of the microbeads against leaching. X-ray diffraction, inductively coupled plasma atomic emission spectroscopy, thermogravimetric analysis, scanning electron microscopy, transmission electron microscopy, and optical microscopy are used for bead characterization. The beads form a magnetic composite consisting of ∼500 nm-sized crosslinked polymeric microspheres, embedding ∼8 nm γ-Fe2O3 nanoparticles. This nanocomposite shows large room temperature magnetization (∼24 emu/g) due to the high content of maghemite (∼45 wt %) and resistance against leaching even in acidic media. Moreover, the presence of superficial chloromethyl groups is probed by Fourier transform infrared and X-ray photoelectron spectroscopy. The nanocomposite beads displaying chloromethyl groups can be used to selectively remove aminated compounds that are adsorbed on the beads, as is shown here for the molecular separation of 4-aminobenzoic acid from a mixture with benzoic acid. The high magnetization of the composite beads makes them suitable for in situ molecular separations in environmental and biological applications.

Manganese ferrite-based nanoparticles induce ex vivo, but not in vivo, cardiovascular effects.

Magnetic nanoparticles (MNPs) have been used for various biomedical applications. Importantly, manganese ferrite-based nanoparticles have useful magnetic resonance imaging characteristics and potential for hyperthermia treatment, but their effects in the cardiovascular system are poorly reported. Thus, the objectives of this study were to determine the cardiovascular effects of three different types of manganese ferrite-based magnetic nanoparticles: citrate-coated (CiMNPs); tripolyphosphate-coated (PhMNPs); and bare magnetic nanoparticles (BaMNPs). The samples were characterized by vibrating sample magnetometer, X-ray diffraction, dynamic light scattering, and transmission electron microscopy. The direct effects of the MNPs on cardiac contractility were evaluated in isolated perfused rat hearts. The CiMNPs, but not PhMNPs and BaMNPs, induced a transient decrease in the left ventricular end-systolic pressure. The PhMNPs and BaMNPs, but not CiMNPs, induced an increase in left ventricular end-diastolic pressure, which resulted in a decrease in a left ventricular end developed pressure. Indeed, PhMNPs and BaMNPs also caused a decrease in the maximal rate of left ventricular pressure rise (+dP/dt) and maximal rate of left ventricular pressure decline (-dP/dt). The three MNPs studied induced an increase in the perfusion pressure of isolated hearts. BaMNPs, but not PhMNPs or CiMNPs, induced a slight vasorelaxant effect in the isolated aortic rings. None of the MNPs were able to change heart rate or arterial blood pressure in conscious rats. In summary, although the MNPs were able to induce effects ex vivo, no significant changes were observed in vivo. Thus, given the proper dosages, these MNPs should be considered for possible therapeutic applications.

Fabrication of glycine-functionalized maghemite nanoparticles for magnetic removal of copper from wastewater.

Maghemite nanoparticles (MNPs) were functionalized with glycine, by a cost-effective and environmentally friendly procedure, as an alternative route to typical amine-functionalized polymeric coatings, for highly efficient removal of copper ions from water. MNPs were synthesized by co-precipitation method and adsorption of glycine was investigated as a function of ligand concentration and pH. The efficiency of these functionalized nanoparticles for removal of Cu(2+) from water has been explored and showed that adsorption is highly dependent of pH and that it occurs either by forming chelate complexes and/or by electrostatic interaction. The adsorption process, which reaches equilibrium in few minutes and fits a pseudo second-order model, follows the Langmuir adsorption model with a very high maximum adsorption capacity for Cu(2+) of 625mg/g. Furthermore, these nanoadsorbents can be used as highly efficient separable and reusable materials for removal of toxic metal ions.

Effect of magnetic dipolar interactions on nanoparticle heating efficiency: implications for cancer hyperthermia.

Nanostructured magnetic systems have many applications, including potential use in cancer therapy deriving from their ability to heat in alternating magnetic fields. In this work we explore the influence of particle chain formation on the normalized heating properties, or specific loss power (SLP) of both low- (spherical) and high- (parallelepiped) anisotropy ferrite-based magnetic fluids. Analysis of ferromagnetic resonance (FMR) data shows that high particle concentrations correlate with increasing chain length producing decreasing SLP. Monte Carlo simulations corroborate the FMR results. We propose a theoretical model describing dipole interactions valid for the linear response regime to explain the observed trends. This model predicts optimum particle sizes for hyperthermia to about 30% smaller than those previously predicted, depending on the nanoparticle parameters and chain size. Also, optimum chain lengths depended on nanoparticle surface-to-surface distance. Our results might have important implications to cancer treatment and could motivate new strategies to optimize magnetic hyperthermia.

Magnetic ionic liquids produced by the dispersion of magnetic nanoparticles in 1-n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (BMI.NTf2).

̀This paper reports on the advancement of magnetic ionic liquids (MILs) as stable dispersions of surface-modified γ-Fe(2)O(3), Fe(3)O(4), and CoFe(2)O(4) magnetic nanoparticles (MNPs) in a hydrophobic ionic liquid, 1-n-butyl 3-methylimidazolium bis(trifluoromethanesulfonyl)imide (BMI.NTf(2)). The MNPs were obtained via coprecipitation and were characterized using powder X-ray diffraction, transmission electron microscopy, Raman spectroscopy and Fourier transform near-infrared (FT-NIR) spectroscopy, and magnetic measurements. The surface-modified MNPs (SM-MNPs) were obtained via the silanization of the MNPs with the aid of 1-butyl-3-[3-(trimethoxysilyl)propyl]imidazolium chloride (BMSPI.Cl). The SM-MNPs were characterized by Raman spectroscopy and Fourier transform infrared-attenuated total reflectance (FTIR-ATR) spectroscopy and by magnetic measurements. The FTIR-ATR spectra of the SM-MNPs exhibited characteristic absorptions of the imidazolium and those of the Fe-O-Si-C moieties, confirming the presence of BMSPI.Cl on the MNP surface. Thermogravimetric analysis (TGA) showed that the SM-MNPs were modified by at least one BMSPI.Cl monolayer. The MILs were characterized using Raman spectroscopy, differential scanning calorimetry (DSC), and magnetic measurements. The Raman and DSC results indicated an interaction between the SM-MNPs and the IL. This interaction promotes the formation of a supramolecular structure close to the MNP surface that mimics the IL structure and is responsible for the stability of the MIL. Magnetic measurements of the MILs indicated no hysteresis. Superparamagnetic behavior and a saturation magnetization of ~22 emu/g could be inferred from the magnetic measurements of a sample containing 50% w/w γ-Fe(2)O(3) SM-MNP/BMI.NTf(2).

Ionic liquids as recycling solvents for the synthesis of magnetic nanoparticles.

This work describes an easy synthesis (one pot) of MFe(2)O(4) (M = Co, Fe, Mn, and Ni) magnetic nanoparticles MNPs by the thermal decomposition of Fe(Acac)(3)/M(Acac)(2) by using BMI·NTf(2) (1-n-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) or BMI·PF(6) (1-n-butyl-3-methylimidazolium hexafluorophosphate) ionic liquids (ILs) as recycling solvents and oleylamine as the reducing and surface modifier agent. The effects of reaction temperature and reaction time on the features of the magnetic nanomaterials (size and magnetic properties) were investigated. The growth of the MNPs is easily controlled in the IL by adjusting the reaction temperature and time, as inferred from Fe(3)O(4) MNPs obtained at 150 °C, 200 °C and 250 °C with mean diameters of 8, 10 and 15 nm, respectively. However, the thermal decomposition of Fe(Acac)(3) performed in a conventional high boiling point solvent (diphenyl ether, bp 259 °C), under a similar Fe to oleylamine molar ratio used in the IL synthesis, does not follow the same growth mechanism and rendered only smaller NPs of 5 nm mean diameter. All MNPs are covered by at least one monolayer of oleylamine making them readily dispersible in non-polar solvents. Besides the influence on the nanoparticles growth, which is important for the preparation of highly crystalline MNPs, the IL was easily recycled and has been used in at least 20 successive syntheses.