Interaction of ZnO Nanostructures with Proteins: In Vitro Fibrillation/Antifibrillation Studies and in Silico Molecular Docking Simulations

Protein amyloidosis is related to many neurological disorders. Nanoparticles (NPs) due to their small size can regulate both the polypeptide monomers/oligomers assembly into amyloid fibrils/plaques and the disintegration of the existent plaques. Herein, we have synthesized ZnO nanoflowers and polyol-coated ZnO NPs of relatively small size (40 nm) with cylindrical shape, through solvothermal and microwave-assisted routes, respectively. The effect of the different morphology of nanostructures on the fibrillation/antifibrillation process was monitored in bovine serum albumin (BSA) and human insulin (HI) by fluorescence Thioflavin T (ThT) measurements. Although both nanomaterials affected the amyloid formation mechanism as well as their disaggregation, ZnO nanoflowers with their sharp edges exhibited the greatest amyloid degradation rate in both model proteins (73% and 35%, respectively) and inhibited the most the insulin fibril growth, while restrained also the fibrillation process in the case of albumin solution. In silico molecular docking simulations on the crystal structure of BSA and HI were performed to analyze further the observed in vitro activity of ZnO nanostructures. The binding energy of ZnO NPs was found lower for BSA (−5.44), highlighting their ability to act as catalysts in the fibrillation process of albumin monomers

Tailoring Ca-Based Nanoparticles by Polyol Process for Use as Nematicidals and pH Adjusters in Agriculture

The remarkable progress in nanotechnology has extended the application of inorganic nanoparticles (NPs) in the agriculture sector, as both economically sustainable and environmentally sound alternatives. Root knot nematodes are undoubtedly a foremost problem of agriculture, and research strives to develop effective materials to tackle this issue. Herein, the microwave-assisted selective polyol synthesis of different compositions of Ca-based NPs, Ca(OH)2, Ca(OH)2/CaCO3, and CaCO3 is reported and the products were evaluated as nematicides and pH adjusters. Two precursors (CaCl2 and Ca(NO3)2) and three polyols (1,2-propylene glycol (PG), tetraethylene glycol (TEG), polyethylene glycol (PEG 8000)) that differ in their redox potential have been utilized to provide selectivity over composition. On the basis of the utilized polyols, NPs are produced as inorganic/organic hybrid formulations with a biocompatible organic coating that provides increased colloidal stability and controlled release of active components. Characterization of NPs has been carried out by XRD, TGA, FTIR, TEM, and pH-metry. Each composition exhibited different pH changing ability, an essential feature for agrochemical applications. The in vitro nematicidal activity of Ca(OH)2, Ca(OH)2/CaCO3, and CaCO3NPs was evaluated on second stage juveniles (J2) of two Meloidogyne species (Meloidogyne incognita and Meloidogyne javanica) based on nematode paralysis experiments. Results unveiled nematicidal activity for all evaluated Ca-based NPs, while Ca(OH)2 and CaCO3 NPs appeared to be the most and the least effective ones, respectively. The nematicidal effect appears to be boosted by the release of [OH]- anions, as indicated by pH-metric measurements, displaying the crucial role of [OH]- anions in their nematicidal activity

The Effect of Fused 12-Membered Nickel Metallacrowns on DNA and their Antibacterial Activity

The synthesis, characterization and the biological study of a series of Ni(ll)2(carboxylato)2 [12- MCNi(II)N(shi)2(pko)2-4][12-MCNi(ii)N(sh03(pko)-4] (CH3OH)3(H3O) fused 12-membered metallacrowns with 10 metal ions and commercial available herbicides or anti-inflammatory drugs as carboxylato ligands are reported. All the compounds have a mixed ligand composition with salicylhydroxamic acid and di-2-pyridylketonoxime as chelate agents. The compounds construct metallacrown cores {[12-MCNi(n)N(sj02(pko)2-4][12-MCNi(ll)N(shO3(pko)-4]}2+ following the pattern [-Ni-O-N-]4. The neutral decanuclear [Ni(II)(A)]2[12-MCNi(II)N(shi)2(pko)2-4][12-MCNi(II)N(pko)3(pko)-4] fused metallacrown, consists of two [12-MCM(ox)N(ligand)-4] units the {Ni(ll)(A)[12-MCNi(II)N(shi)2(pko)2-4]} and {Ni(II)(A)[12-MCNi(II)N(shi)3(pko)-4]} with 1+ and 1- charge, respectively. Each metallacrown unit has four ring Ni(II) ions and one additional encapsulated Ni(II) ion in planar arrangement. The anionic unit is bonded with cationic one creating binuclear moieties. The herbicide or antiiflammatory carboxylato ligands are bridging the central octahedral nickel atom with a ring metal ion in a bindetate fashion. The effect on DNA and their antibacterial activity was examined. The changes in the mobility can be attributed to the altered structures of the pDNA treated with Ni(II) complexes. Evaluating the data of the antibacterial activity of the compounds tested, we can conclude that nickel complexes present strong antibacterial activity

Structure Differentiation of Hydrophilic Brass Nanoparticles Using a Polyol Toolbox

Nano-brasses are emerging as a new class of composition-dependent applicable materials. It remains a challenge to synthesize hydrophilic brass nanoparticles (NPs) and further exploit them for promising bio-applications. Based on red/ox potential of polyol and nitrate salts precursors, a series of hydrophilic brass formulations of different nanoarchitectures was prepared and characterized. Self-assembly synthesis was performed in the presence of triethylene glycol (TrEG) and nitrate precursors Cu(NO3)2·3H2O and Zn(NO3)2·6H2O in an autoclave system, at different temperatures, conventional or microwave-assisted heating, while a range of precursor ratios was investigated. NPs were thoroughly characterized via X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), transmition electron microscopy (TEM), Fourier-transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), and ζ-potential to determine the crystal structure, composition, morphology, size, state of polyol coating, and aqueous colloidal stability. Distinct bimetallic α-brasses and γ-brasses, α-Cu40Zn25/γ-Cu11Zn24, α-Cu63Zn37, α-Cu47Zn10/γ-Cu19Zn24, and hierarchical core/shell structures, α-Cu59Zn30@(ZnO)11, Cu35Zn16@(ZnO)49, α-Cu37Zn18@(ZnO)45, Cu@Zinc oxalate, were produced by each synthetic protocol as stoichiometric, copper-rich, and/or zinc-rich nanomaterials. TEM sizes were estimated at 20–40 nm for pure bimetallic particles and at 45–70 nm for hierarchical core/shell structures. Crystallite sizes for the bimetallic nanocrystals were found ca. 30–45 nm, while in the case of the core-shell structures, smaller values around 15–20 nm were calculated for the ZnO shells. Oxidation and/or fragmentation of TrEG was unveiled and attributed to the different fabrication routes and formation mechanisms. All NPs were hydrophilic with 20–30% w/w of polyol coating, non-ionic colloidal stabilization (−5 mV < ζ-potential < −13 mV) and relatively small hydrodynamic sizes (<250 nm). The polyol toolbox proved effective in tailoring the structure and composition of hydrophilic brass NPs while keeping the crystallite and hydrodynamic sizes fixed

Synthesis and biological evaluation of PEGylated CuO nanoparticles

There is a growing field of research into the physicochemical properties of metal oxide nanoparticles (NPs) and their potential use against tumor formation, development and progression. Coated NPs with biocompatible surfactants can be incorporated into the natural metabolic pathway of the body and specifically favor delivery to the targeted cancerous cells versus normal cells. Polyethylene glycol (PEG) is an FDA approved, biocompatible synthetic polymer and PEGylated NPs are regarded as “stealth” nanoparticles, which are not recognized by the immune system. Herein, PEGylated cupric oxide nanoparticles (CuO NPs) with either PEG 1000 or PEG 8000 were hydrothermally prepared upon properly adjusting the reaction conditions. Depending on the reaction time CuO NPs in the range of core sizes 11–20 nm were formed, while hydrodynamic sizes substantially varied (330–1120 nm) with improved colloidal stability in PBS. The anticancer activity of the NPs was evaluated on human cervical carcinoma HeLa cells by using human immortalized embryonic kidney 293 FT cells as a control. Viability assays (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT) revealed that CuO NPs could selectively reduce viability of tumor cells (IC50 values 11.91–25.78 μg/mL). Reactive oxygen species (ROS) production, cell membrane damage and apoptotic DNA laddering were also evident by nitroblue tetrazolium (NBT) reduction, lactate dehydrogenase (LDH) release assays and DNA electrophoresis, respectively. CuO NPs strongly inhibited lipoxygenase (LOX) enzymatic activity with IC50 values 4–5.9 μg/mL, highlighting in that manner their anti-inflammatory activity

Elucidation of One Step Synthesis of PEGylated CuFe Bimetallic Nanoparticles. Antimicrobial Activity of CuFe@PEG vs Cu@PEG

There is a growing field of research on the physicochemical properties of bimetallic nanoparticles (BMNPs) and their potential use in different applications. Meanwhile, their antimicrobial activity is scarcely reported, although BMNPs can potentially achieve unique chemical transformations and synergetic effects can be presented. Towards this direction a reproducible simple hybrid polyol process under moderate temperature solvothermal conditions has been applied for the isolation of non-oxide contaminated bimetallic CuFe nanoparticles (NPs). 1,2-propylene glycol (PG), tetraethylene glycol (TEG) and polyethylene glycol (PEG 8000), that exhibit different physicochemical properties, have been utilized to regulate the size, structure, composition and the surface chemistry of NPs. The BMNPs were found to be of small crystalline size, 30–45 nm, and high hydrophilicity, different wt% percentage of organic coating and variable hydrodynamic size and surface charge. The antimicrobial activity of the BMNPs was evaluated against the bacterial strains B. subtilis, E. coli and fungus S. cerevisiae. The IC50 values for CuFe NPs were found significantly lower compared with Cu NPs of the same size, revealing an enhancement in the antimicrobial activity when iron and copper coexist in the crystal structure. The reactive oxygen species (ROS) production was measured intracellularly and extracellularly by the nitroblue tetrazolium assay in the fungal cultures. No extracellular ROS were measured suggesting that both CuFe and Cu NPs enter the fungal cells during the incubation, also verified by optical imaging of the fungal cells in the presence of NPs. Higher ROS concentrations were generated intracellularly for CuFe NPs supporting different red/ox reaction mechanisms

Conditions determining the morphology and nanoscale magnetism of Co nanoparticles: Experimental and numerical studies

Co-based nanostructures ranging from core-shell to hollow nanoparticles were produced by varying the reaction time and the chemical environment during the thermal decomposition of Co2(CO)8. Both structural characterization and kinetic model simulation illustrate that the diffusivities of Co and oxygen determine the growth ratio and the final morphology of the nanoparticles. Exchange coupling between Co and Co-oxide in core/shell nanoparticles induced a shift of field-cooled hysteresis loops that is proportional to the shell thickness, as verified by numerical studies. The increased nanocomplexity when going from core/shell to hollow particles, also leads to the appearance of hysteresis above 300 K due to an enhancement of the surface anisotropy resulting from the additional spin-disordered surfaces.Comment: 29 pages including 11 figures embedded. Submitted to Phys. Rev.

Magnetic hyperthermia efficiency and MRI contrast sensitivity of colloidal soft/hard ferrite nanoclusters

The use of magnetic nanostructures as theranostic agents is a multiplex task as physiochemical and biochemical properties including excellent magneto-responsive properties, low toxicity, colloidal stability and facile surface engineering capability are all required. Nonetheless, much progress has been made in recent years synthesis of “all-in-one” MNPs remain unambiguously challenging. Towards this direction, in this study is presented a facile incorporation of a soft magnetic phase (MnFe2O4 NPs) with a hard phase (CoFe2O4 NPs) in the presence of the biocompatible polymer sodium dodecyl sulfate (SDS), into spherical and compact bi-magnetic nanoclusters (NCs) with modulated magnetic properties that critically enhance hyperthermic efficiency and MRI contrast effect. Hydrophobic MnFe2O4 and CoFe2O4 NPs coated with oleylamine of the same size (9 nm) were used as primary building units for the formation of the bi-magnetic NCs through a microemulsion approach where a set of experiments were conducted to identify the optimal concentration of SDS (19.5 mM) for the cluster formation. Additionally, homo-magnetic NCs of MnFe2O4 NPs and CoFe2O4 NPs, respectively were synthesized for comparative studies. The presence of distinct magnetic phases within the bi-magnetic NCs resulting in synergistic behavior, where the soft phase offers moderate coercivity Hc and the hard one high magnetization Ms. Increased specific loss power (SLP) value was obtained for the bi-magnetic system (525 W/g) when compared with the homo-magnetic NCs (104 W/g for MnNCs and 223 W/g for CoNCs) under field conditions of 25 kA/m and 765 kHz. Relaxivities (r2) of the bi-magnetic NCs were also higher (81.8 mM−1 s−1) than those of the homo-magnetic NCs (47.4 mM−1 s−1 for MnNCs and 3.1 mM−1 s−1 for CoNCs), while the high r2/r1 value renders the system suitable for T2-weighted MRI imaging

Paclitaxel Magnetic Core⁻Shell Nanoparticles Based on Poly(lactic acid) Semitelechelic Novel Block Copolymers for Combined Hyperthermia and Chemotherapy Treatment of Cancer.

Magnetic hybrid inorganic/organic nanocarriers are promising alternatives for targeted cancer treatment. The present study evaluates the preparation of manganese ferrite magnetic nanoparticles (MnFe2O4 MNPs) encapsulated within Paclitaxel (PTX) loaded thioether-containing ω-hydroxyacid-co-poly(d,l-lactic acid) (TEHA-co-PDLLA) polymeric nanoparticles, for the combined hyperthermia and chemotherapy treatment of cancer. Initially, TEHA-co-PDLLA semitelechelic block copolymers were synthesized and characterized by 1H-NMR, FTIR, DSC, and XRD. FTIR analysis showed the formation of an ester bond between the two compounds, while DSC and XRD analysis showed that the prepared copolymers were amorphous. MnFe2O4 MNPs of relatively small crystallite size (12 nm) and moderate saturation magnetization (64 emu·g-1) were solvothermally synthesized in the sole presence of octadecylamine (ODA). PTX was amorphously dispersed within the polymeric matrix using emulsification/solvent evaporation method. Scanning electron microscopy along with energy-dispersive X-ray spectroscopy and transmission electron microscopy showed that the MnFe2O4 nanoparticles were effectively encapsulated within the drug-loaded polymeric nanoparticles. Dynamic light scattering measurements showed that the prepared nanoparticles had an average particle size of less than 160 nm with satisfactory yield and encapsulation efficiency. Diphasic PTX in vitro release over 18 days was observed while PTX dissolution rate was mainly controlled by the TEHA content. Finally, hyperthermia measurements and cytotoxicity studies were performed to evaluate the magnetic response, as well as the anticancer activity and the biocompatibility of the prepared nanocarriers