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    Graphene oxide functional nanohybrids with magnetic nanoparticles for improved vectorization of doxorubicin to neuroblastoma cells
    (Basel : MDPI AG, 2019) Lerra, L.; Farfalla, A.; Sanz, B.; Cirillo, G.; Vittorio, O.; Voli, F.; Grand, M.L.; Curcio, M.; Nicoletta, F.P.; Dubrovska, A.; Hampel, S.; Iemma, F.; Goya, G.F.
    With the aim to obtain a site-specific doxorubicin (DOX) delivery in neuroblastoma SH-SY5Y cells, we designed an hybrid nanocarrier combining graphene oxide (GO) and magnetic iron oxide nanoparticles (MNPs), acting as core elements, and a curcumin–human serum albumin conjugate as functional coating. The nanohybrid, synthesized by redox reaction between the MNPs@GO system and albumin bioconjugate, consisted of MNPs@GO nanosheets homogeneously coated by the bioconjugate as verified by SEM investigations. Drug release experiments showed a pH-responsive behavior with higher release amounts in acidic (45% at pH 5.0) vs. neutral (28% at pH 7.4) environments. Cell internalization studies proved the presence of nanohybrid inside SH-SY5Y cytoplasm. The improved efficacy obtained in viability assays is given by the synergy of functional coating and MNPs constituting the nanohybrids: while curcumin moieties were able to keep low DOX cytotoxicity levels (at concentrations of 0.44–0.88 µM), the presence of MNPs allowed remote actuation on the nanohybrid by a magnetic field, increasing the dose delivered at the target site.
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    Magnetic Graphene Oxide Nanocarrier for Targeted Delivery of Cisplatin : A Perspective for Glioblastoma Treatment
    (Basel : MDPI, 2019) Makharza, Sami A.; Cirillo, Giuseppe; Vittorio, Orazio; Valli, Emanuele; Voli, Florida; Farfalla, Annafranca; Curcio, Manuela; Iemma, Francesca; Nicoletta, Fiore Pasquale; El-Gendy, Ahmed A.; Goya, Gerardo F.; Hampel, Silke
    Selective vectorization of Cisplatin (CisPt) to Glioblastoma U87 cells was exploited by the fabrication of a hybrid nanocarrier composed of magnetic γ-Fe2 O3 nanoparticles and nanographene oxide (NGO). The magnetic component, obtained by annealing magnetite Fe3 O4 and characterized by XRD measurements, was combined with NGO sheets prepared via a modified Hummer’s method. The morphological and thermogravimetric analysis proved the effective binding of γ-Fe2 O3 nanoparticles onto NGO layers. The magnetization measured under magnetic fields up to 7 Tesla at room temperature revealed superparamagnetic-like behavior with a maximum value of MS = 15 emu/g and coercivity HC ≈ 0 Oe within experimental error. The nanohybrid was found to possess high affinity towards CisPt, and a rather slow fractional release profile of 80% after 250 h. Negligible toxicity was observed for empty nanoparticles, while the retainment of CisPt anticancer activity upon loading into the carrier was observed, together with the possibility to spatially control the drug delivery at a target site. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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    Effects of new beta-type Ti-40Nb implant materials, brain-derived neurotrophic factor, acetylcholine and nicotine on human mesenchymal stem cells of osteoporotic and non osteoporotic donors
    (San Francisco, CA : Public Library of Science (PLoS), 2018) Kauschke, V.; Gebert, A.; Calin, M.; Eckert, J.; Scheich, S.; Heiss, C.; Lips, K.S.
    Introduction Treatment of osteoporotic fractures is still challenging and an urgent need exists for new materials, better adapted to osteoporotic bone by adjusted Young’s modulus, appropriate surface modification and pharmaceuticals. Materials and methods Titanium-40-niobium alloys, mechanically ground or additionally etched and titanium-6-alu-minium-4-vanadium were analyzed in combination with brain-derived neurotrophic factor, acetylcholine and nicotine to determine their effects on human mesenchymal stem cells in vitro over 21 days using lactate dehydrogenase and alkaline phosphatase assays, live cell imaging and immunofluorescence microscopy. Results Cell number of human mesenchymal stem cells of osteoporotic donors was increased after 14 d in presence of ground titanium-40-niobium or titanium-6-aluminium-4-vanadium, together with brain-derived neurotrophic factor. Cell number of human mesenchymal stem cells of non osteoporotic donors increased after 21 d in presence of titanium-6-aluminium-4-vanadium without pharmaceuticals. No significant increase was measured for ground or etched titanium-40-niobium after 21 d. Osteoblast differentiation of osteoporotic donors was significantly higher than in non osteoporotic donors after 21 d in presence of etched, ground titanium-40-niobium or titanium-6-aluminium-4-vanadium accompanied by all pharmaceuticals tested. In presence of all alloys tested brain-derived neurotrophic factor, acetylcholine and nicotine increased differentiation of cells of osteoporotic donors and accelerated it in non osteoporotic donors. Conclusion We conclude that ground titanium-40-niobium and brain-derived neurotrophic factor might be most suitable for subsequent in vivo testing.
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    Surface defects reduce Carbon Nanotube toxicity in vitro
    (Amsterdam [u.a.] : Elsevier Science, 2019) Requardt, Hendrik; Braun, Armin; Steinberg, Pablo; Hampel, Silke; Hansen, Tanja
    The cytotoxicity of two different types of Multi-walled Carbon Nanotubes (MWCNTs)in A549 lung epithelial cells and HepG2 hepatocytes was investigated. One MWCNT still contained iron that was used as a catalyst during production, while the other one had all iron removed in a post-production heat treatment resulting in significantly fewer surface defects. The WST-8 assay was applied to test cell viability. To check the integrity of the cell membrane, we performed the lactate dehydrogenases assay (LDH)and measured the cellular production of reactive oxygen species (ROS). Finally, to examine cell proliferation, we conducted a cell cycle analysis. The results showed a dose- and time-dependent decrease in cell viability for both MWCNTs in both cell types. Moreover, a dose- and time-dependent increase in LDH leakage was detected, thereby indicating a decreased membrane integrity. The production of ROS was significantly increased in the case of the heat-treated MWCNTs. The heat-treated MWCNTs showed significantly stronger adverse effects when compared to the non-treated MWCNTs. Additionally, the heat-treated MWCNTs induced a dose-dependent cell cycle arrest in A549 cells. Both MWCNTs induced a significant cytotoxicity, whereby the heat treatment, leading to a decrease in surface defects, further increased the indicated adverse effects. © 2019 The Authors