Selective synthesis of Cu2O and Cu/Cu2O NPs: antifungal activity to yeast Saccharomyces cerevisiae and DNA interaction.

A facile selective synthesis of Cu2O and heterogeneous Cu/Cu2O nanoparticles (NPs) was achieved through a solvothermal approach by Cu(NO3)2 in proportion of three different surfactants, namely, tetraethylene glycol (TEG), oleylamine (OAm) and polyoxyethylene (20) sorbitan laurate (Tween 20). Formation aspects for the spherical Cu2O@OAm (30 nm) and Cu2O@Tween (12 nm) as well as for the core-shell and semishell Cu/Cu2O@TEG NPs (7 nm) and the Cu/Cu2O@OAm (170 nm) nanorods have been proposed. The fungistatic and fungicidal activity of the newly synthesized NPs was studied in vitro against the yeast Saccharomyces cerevisiae, which constitutes a unicellular eukaryotic model microorganism in molecular and cell biology. The antifungal results, based on optical density and fluorescence measurements, clearly indicate that the composition, size, and amount of surfactant are of key importance in the antifungal properties of the NPs. Cu2O@OAm NPs exhibited the most prominent antifungal activity with 3.73 µg/mL IC(50viability) value. The isolated DNA of S. cerevisiae cells after exposure to the NPs was investigated, and binding and/or degradation phenomena were recorded that are correlated to the size and concentration of the NPs. Their activity pathway was further explored, and reactive oxygen species production and lipid peroxidation were verified mainly for Cu2O NPs.

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, 30-45nm, 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.

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 11-20nm were formed, while hydrodynamic sizes substantially varied (330-1120nm) 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 11.91-25.78µg/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 4-5.9µg/mL, highlighting in that manner their anti-inflammatory activity.

Hetero-nanocomposites of magnetic and antifungal nanoparticles as a platform for magnetomechanical stress induction in Saccharomyces cerevisiae.

Copper(i) oxide (Cu2O) nanoparticles (NPs) of 30 nm with antifungal properties have been functionalized with 9 nm nickel ferrite (NiFe2O4) magnetic nanoparticles (MNPs) to construct hetero-nanocomposites (NCs) of a submicron hydrodynamic size for magnetomechanical stress induction in the yeast, Saccharomyces cerevisiae. A post-synthetic approach involving the assembly through hydrophobic interactions of the preformed NPs of non-uniform sizes, albeit coated with the same surfactant (oleylamine), is reported. Solvents of different polarity were implemented during the synthetic procedure resulting in NCs of similar composition consisting mainly of MNPs randomly decorated onto the bigger Cu2O NPs. The antifungal properties of the building NPs and the NCs were studied in terms of fungistatic and fungicidal activity, whereas the ionic leaching was found to be negligible, highlighting the nanosize effect. Although S. cerevisiae cells were found to be resistant to individual NiFe2O4 MNPs because of their small size, their sensitivity to NCs significantly increased upon short-time exposure to a rotating low-frequency magnetic field (10 min, 30 Hz, 35 G) and this arises from the collective properties. The magnetomechanical cell stress induction was accompanied by alteration of cellular membrane integrity and programmed cell death signaling.

Hydrothermal synthesis of copper based nanoparticles: antimicrobial screening and interaction with DNA.

Copper based nanoparticles (Cu-based NPs) of different compositions and sizes have been hydrothermally synthesized by varying the reaction time in the presence of the biocompatible surfactants polyoxyethylene (20) sorbitan laurate (Tween 20) and polyethylene glycol 8000 (PEG 8000). Effective control of the above synthetic parameters gave rise to Cu, Cu2O and Cu/Cu2O NPs of 10-44 nm. The antibacterial activity of the NPs was screened against Gram-positive (Bacillus subtilis, Bacillus cereus, Staphylococcus aureus) and Gram-negative (Xanthomonas campestris, Escherichia coli) bacteria. The Cu-based NPs induce pDNA degradation in a dose-dependent manner as well as extensive ds CT-DNA degradation. Cu2O NPs of 16 nm and 12 nm exhibit the lowest IC50 values (2.13 µg/mL and 3.7 µg/mL) against B. cereus and B. subtilis, respectively. The agarose gel electrophoresis of ds CT-DNA treated with Cu2O NPs demonstrated degradation at high concentration. In lower concentrations, viscosity measurements indicated groove binding. In regard to the enhanced antibacterial effect and specificity of Cu2O NPs against the Gram-positive strains, the activity pathway was further explored and ROS production and lipid peroxidation verified. The released copper ions 5.15 mg/L in distilled water and 16.32 mg/L in nutrient medium, found below the critical value to inhibit bacterial growth and thus nanosized composition effect is predominant.