NMR relaxometric properties and cytotoxicity of Gd2O3 nanoparticle suspensions in an organic liquid

Gd2O3 nanoparticles and their agglomerates from approximately 10 to 80 nm in size suspended in an organic liquid were synthesized via polyol route. The reaction between diethylene glycol and added acetic acid, which occurred simultaneously with the synthesis of Gd2O3 nanoparticles, was catalyzed by sodium bisulfate to transform as much as possible diethylene glycol in corresponding ester at the end of complete reaction. The produced nanosized material of gadolinium oxide was investigated by TEM, DLS, FTIR spectroscopy, and NMR relaxometry. Biological evaluation of this material was done by MTT and crystal violet assays to determine the cell viability. Longitudinal and transverse relaxivities of water-diluted Gd2O3 nanoparticle suspensions estimated to be r(1) = 13.6 and r(2) = 14.7 s(-1) mM(-1) are about three times higher compared to the relaxivities obtained for standard contrast agent Gd-DTPA (Magnevist). Good MRI signal intensities of the water-diluted Gd2O3 nanoparticle suspensions were recorded in the Gd concentration range 0.2-0.3 mM for which the suspensions were not toxic exhibiting simultaneously higher signal intensities than those for Magnevist in the Gd concentration range 0.4-1 mM for which this standard contrast agent was not toxic. These properties make the produced Gd2O3 nanoparticle material promising for potential application as MRI contrast agent

Gd2O3 nanoparticles stabilized by hydrothermally modified dextrose for positive contrast magnetic resonance imaging

w Gd2O3 nanoparticles of a few nm in size and their agglomerates dispersed in dextrose derived polymer template were synthesized by hydrothermal treatment. The produced nanosized material was investigated by TEM, FTIR spectroscopy, SQUID measurements and NMR relaxometry. Biological evaluation of this material was done by crystal violet and MTT assays to determine the cell viability. Longitudinal and transverse NMR relaxivities of water diluted Gd2O3 nanoparticle dispersions measured at the magnetic field of 1.5 T, estimated to be r(1)(Gd2O3)=9.6 s(-1) mM(-1) in the Gd concentration range 0.1-30 mM and r(2)(Gd2O3)=17.7 s(-1) mM(-1) in the lower concentration range 0.1-0.8 mM, are significantly higher than the corresponding relaxivities measured for the standard contrast agent r1 (Gd-DTPA)=4.1 s(-1) mM(-1) and r(2)(Gd-DTPA)= 5.1 s(-1) mM(-1). The ratio of the two relaxivities for Gd2O3 nanoparticles r(2)/r(1) = 1.8 is suitable for T-1-weighted imaging. Good MRI signal intensities of the water diluted Gd2O3 nanoparticle dispersions were recorded at lower Gd concentrations 0.2-0.8 mM. The Gd2O3 samples did not exert any significant cytotoxic effects at Gd concentrations of 0.2 mM and below. These properties of the produced Gd2O3 nanoparticles in hydrothermally modified dextrose make them promising for potential application in MRI for the design of a positive MRI contrast agent. (C) 2015 Elsevier B.V. All rights reserved

Ultrasmall iron oxide nanoparticles: Magnetic and NMR relaxometric properties

Ultrasmall iron oxide (USPIO) nanoparticles, with diameter mostly less than 3 nm dispersed in an organic carrier fluid were synthesized by polyol route. The evolution of ZFC-FC magnetization curves with temperature, as well as the shift of the ac susceptibility peaks upon changing the frequency, reveal that the nanoparticles in the fluid are non-interacting and superparamagnetic with the blocking temperature T-B similar to 10 K. The Mossbauer spectra analysis proposed the core/shell structure of the nanoparticles consisting of stoichiometric gamma-Fe2O3 core and non-stoichiometric shell. The nanoparticle surface layer has a great influence on their properties which is principally manifested in significant reduction of the magnetization and in a large increase in magnetic anisotropy. Magnetic moments do not saturate in fields up to 5 T, even at the lowest measured temperature, T = 5 K. The average magnetic particle diameter is changed from 1.3 to 1.8 nm with increasing magnetic field from 0 to 5 T which is noticeably smaller than the particle sizes measured by TEM. The estimated effective magnetic anisotropy constant value, K-eff = 2 x 10(5) J/m(3), is two orders of magnitude higher than in the bulk maghemite. Measurements of the longitudinal and transverse NMR relaxivity parameters on water diluted nanoparticle dispersions at 1.5 T gave the values r(1) = 0.028 mmol(-1) s(-1), r(2) = 0.050 mmol(-1) s(-1) and their ratio r(2)/r(1) = 1.8. Continuous increase of the T-1-weighted MRI signal intensity with increasing Fe concentration in the nanoparticle dispersions was observed which makes this ferrofluid to behave as a positive T-1 contrast agent. (C) 2017 Elsevier B.V. All rights reserved

Photodynamic antibacterial effect of graphene quantum dots

Synthesis of new antibacterial agents is becoming increasingly important in light of the emerging antibiotic resistance. In the present study we report that electrochemically produced graphene quantum dots (GQD), a new class of carbon nanoparticles, generate reactive oxygen species when photoexcited (470 nm, 1 W), and kill two strains of pathogenic bacteria, methicillin-resistant Staphylococcus aureus and Escherichia coli. Bacterial killing was demonstrated by the reduction in number of bacterial colonies in a standard plate count method, the increase in propidium iodide uptake confirming the cell membrane damage, as well as by morphological defects visualized by atomic force microscopy. The induction of oxidative stress in bacteria exposed to photoexcited GQD was confirmed by staining with a redox-sensitive fluorochrome dihydrorhodamine 123. Neither GQD nor light exposure alone were able to cause oxidative stress and reduce the viability of bacteria. Importantly, mouse spleen cells were markedly less sensitive in the same experimental conditions, thus indicating a fairly selective antibacterial photodynamic action of GQD. (C) 2014 Elsevier Ltd. All rights reserved

Graphene quantum dots show protective effect on a model of experimental autoimmune encephalomyelitis

29th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Sep 17-20, 2016, Vienna, Austri

c-Jun N-terminal kinase-dependent apoptotic photocytotoxicity of solvent exchange-prepared curcumin nanoparticles

Indian spice curcumin is known for its anticancer properties, but the anticancer mechanisms of nanoparticulate curcumin have not been completely elucidated. We here investigated the in vitro anticancer effect of blue light (470 nm, 1 W)-irradiated curcumin nanoparticles prepared by tetrahydrofuran/water solvent exchange, using U251 glioma, B16 melanoma, and H460 lung cancer cells as targets. The size of curcumin nanocrystals was approximately 250 nm, while photoexcitation induced their oxidation and partial agglomeration. Although cell membrane in the absence of light was almost impermeable to curcumin nanoparticles, photoexcitation stimulated their internalization. While irradiation with blue light (1-8 min) or nanocurcumin (1.25-10 mu g/ml) alone was only marginally toxic to tumor cells, photoexcited nanocurcumin displayed a significant cytotoxicity depending both on the irradiation time and nanocurcumin concentration. Photoexcited nanocurcumin induced phosphorylation of cJun N-terminal kinase (JNK), mitochondrial depolarization, caspase-3 activation, and cleavage of poly (ADP-ribose) polymerase, indicating apoptotic cell death. Accordingly, pharmacologial inhibition of JNK and caspase activity rescued cancer cells from photoexcited nanocurcumin. On the other hand, antioxidant treatment did not reduce photocytotoxicity of nanocurcumin, arguing against the involvement of oxidative stress. By demonstrating the ability of photoexcited nanocurcumin to induce oxidative-stress independent, JNK-and caspase-dependent apoptosis, our results support its further investigation in cancer therapy

Graphene quantum dots inhibit T cell-mediated neuroinflammation in rats

We investigated the therapeutic capacity of nano-sized graphene sheets, called graphene quantum dots (GQD), in experimental autoimmune encephalomyelitis (EAE), an animal model of immune-mediated central nervous system (CNS) damage. Intraperitoneally administered GQD (10 mg/kg/day) accumulated in the lymph node and CNS cells of Dark Agouti rats in which EAE was induced by immunization with spinal cord homogenate in complete Freund's adjuvant. GQD significantly reduced clinical signs of EAE when applied throughout the course of the disease (day 0–32), while the protection was less pronounced if the treatment was limited to the induction (day 0–7 post-immunization) or effector (from day 8 onwards) phase of the disease. GQD treatment diminished immune infiltration, demyelination, axonal damage, and apoptotic death in the CNS of EAE animals. GQD also reduced the numbers of interferon-γ-expressing T helper (Th)1 cells, as well as the expression of Th1 transcription factor T-bet and proinflammatory cytokines tumor necrosis factor, interleukin-1, and granulocyte-macrophage colony-stimulating factor in the lymph nodes and CNS immune infitrates. The protective effect of GQD in EAE was associated with the activation of p38 and p42/44 mitogen-activated protein kinases (MAPK) and Akt in the lymph nodes and/or CNS. Finally, GQD protected oligodendrocytes and neurons from T cell-mediated damage in the in vitro conditions. Collectively, these data demonstrate the ability of GQD to gain access to both immune and CNS cells during neuroinflammation, and to alleviate immune-mediated CNS damage by modulating MAPK/Akt signaling and encephalitogenic Th1 immune response. © 2018 Elsevier Lt

Large Graphene Quantum Dots Alleviate Immune-Mediated Liver Damage

We investigated the effect of large (40 nm) graphene quantum dots (GQDs) in concanavalin A (Con A; 12 mg/kg i.v.)-induced mouse hepatitis, a T cell-mediated liver injury resembling fulminant hepatitis in humans. Intravenously injected GQDs (50 mg/kg) accumulated in liver and reduced Con A-mediated liver damage, as demonstrated by histopathological analysis and a decrease in liver lipid peroxidation and serum levels of liver transaminases. The cleavage of apoptotic markers caspase-3/PARP and mRNA levels of proapoptotic mediators Puma, Noxa, Bax, Bak1, Bim, Apaf1, and p21, as well as LC3-I conversion to autophagosome-associated LC3-II and expression of autophagy-related (Atg) genes Atg4b, Atg7, Atg12, and beclin-1, were attenuated by GQDs, indicating a decrease in both apoptosis and autophagy in the liver tissue. This was associated with the reduced liver infiltration of immune cells, particularly the T cells producing proinflammatory cytokine IFN-?, and a decrease in IFN-gamma serum levels. In the spleen of GQD-exposed mice, mRNA expression of IFN-? and its transcription factor T-bet was reduced, while that of the IL-33 ligand ST2 was increased. The hepatoprotective effect of GQDs was less pronounced in ST2-deficient mice, indicating that it might depend on ST2 upregulation. In vitro, GQDs inhibited splenocyte IFN-gamma production, reduced the activation of extracellular signal-regulated kinase in macrophage and T cell lines, inhibited macrophage production of the free radical nitric oxide, and reduced its cytotoxicity toward hepatocyte cell line HepG2. Therefore, GQDs alleviate immune-mediated fulminant hepatitis by interfering with T cell and macrophage activation and possibly by exerting a direct hepatoprotective effect