The Level of Anti-Polyethylene Glycol (PEG) Immunoglobulin G Antibodies in Human Serum Does Not Correlate with Efficiency of PEGylated Nanoparticle Uptake by Monocytes.

The presence of anti-polyethylene glycol (PEG) antibodies can limit the clinical efficacy of PEGylated drugs and cause anaphylactic reactions in patients. Monocytes/macrophages are effector cells involved in IgG-mediated passive systemic anaphylaxis. We studied the influence of human blood serum on the efficiency of uptake of PEGylated nanoparticles by human blood monocytes. It has been shown that magnetic nanoparticles modified with PEG-3000 and solid lipid nanoparticles containing PEG-2000 are avidly internalized by human blood monocytes in vitro, the uptake efficiency depends on the features (composition) of donor blood serum, but does not correlate with the level of the IgG antibody against PEG.

Non-magnetic shell coating of magnetic nanoparticles as key factor of toxicity for cancer cells in a low frequency alternating magnetic field.

This work is devoted to studying the effects of non-magnetic shell coating on nanoparticles in a low frequency alternating magnetic field (LF AMF) on tumor cells in vitro. Two types of iron oxide nanoparticles with the same magnetic core with and without silica shells were synthesized. Nanoparticles with silica shells significantly decreased the viability of PC3 cancer cells in a low frequency alternating magnetic field according to the cytotoxicity test, unlike uncoated nanoparticles. We showed that cell death results from the intracellular membrane integrity failure, and the calcium ions concentration increase with the subsequent necrosis. Transmission electron microscopy images showed that the uncoated silica nanoparticles are primarily found in an aggregated form in cells. We believe that uncoated nanoparticles lose their colloidal stability in an acidic endosomal environment after internalization into the cell due to surface etching and the formation of aggregates. As a result, they encounter high endosomal macromolecular viscosity and become unable to rotate efficiently. We assume that effective rotation of nanoparticles causes cell death. In turn, silica shell coating increases nanoparticles stability, preventing aggregation in endosomes. Thus, we propose that the colloidal stability of magnetic nanoparticles inside cells is one of the key factors for effective magneto-mechanical actuation.

Radiolabeled Complex of Antimicrobial Peptides UBI29-41 and UBI18-35 Labeled with 99mTc for Differential Diagnosis of Bone Infection of the Limbs.

We studied an original radiolabeled complex of antimicrobial peptides UBI29-41 and UBI18-35, ubiquicidin derivatives, for distinguishing between bacterial and aseptic inflammation. For radiolabeling of the peptides with technetium-99m, a bifunctional chelating agent succinimide-1-yl 6-(bis(pyridin-2-ylmethyl)amino)hexanoate was used. The obtained complexes 99mТс-DPAH-UBI29-41 and 99mТс-DPAH-UBI18-35 had radiolabeling yield >80% and radiochemical purity >96%. Accumulation of the complexes in the focus of bacterial inflammation in bone structures and the absence of this complex in the site of aseptic inflammation was confirmed in a rat model of traumatic osteomyelitis by single-photon emission computed tomography.

[Superparamagnetic Cobalt Ferrite Nanoparticles "Blow up" Spatial Ordering of Double-stranded DNA Molecules].

The formation of cholesteric liquid-crystalline dispersions formed by double-stranded DNA molecules, handled by positively charged superparamagnetic cobalt ferrite nanoparticles, as well as action of these nanoparticles on DNA dispersion, are considered. The binding of magnetic nanoparticles to the linear double-stranded DNA in solution of high ionic strength (0.3 M NaCl) and subsequent phase exclusion of these complexes from polyethylene glycol-containing solutions lead to their inability to form dispersions, whose particles do possess the spatially twisted arrangement of neighboring double-stranded DNA molecules. The action of magnetic nanoparticles on DNA dispersion (one magnetic nanoparticle per one double-stranded DNA molecule) results in such "perturbation" of DNA structure at sites of magnetic nanoparticles binding that the regular spatial structure of DNA dispersion particles "blows up"; this process is accompanied by disappearance of both abnormal optical activity and characteristic Bragg maximum on the small-angle X-ray scattering curve. Allowing with the fact that the physicochemical properties of the DNA liquid-crystalline dispersion particles reflect features of spatial organization of these molecules in chromosomes of primitive organisms, it is possible, that the found effect can have the relevant biological consequences.

Study of DNA interaction with cobalt ferrite nanoparticles.

Interaction of cobalt ferrite nanopowder and nucleic acid was investigated. Superparamagnetic cobalt ferrite nanoparticles (6-12 nm) were prepared by mechanochemical synthesis. Structure of the nanopowder was characterized using X-ray diffraction. It was shown that cobalt ferrite nanoparticles were associated with ssDNA and dsDNA in Tris-buffer resulting in bionanocomposite formation with mass weight relation nanoparticles: DNA 1:(0.083 +/- 0.003) and 1:(0.075 +/- 0.003) respectively. The mechanism of interaction between a DNA and cobalt ferrite nanoparticles was considered basing on the whole set of obtained data: FTIR-spectroscopy, analyzing desorption of DNA from the surface of the particles while changing the chemical content of the medium, and on the modeling interaction of specific biomolecule fragments with surface of a inorganic material. It was supposed that the linkage was based on coordination interaction of the phosphate groups and oxygen atoms heterocyclic bases of DNA with metal ions on the particle surface. These data can be used to design specific magnetic DNA-nanoparticles hybrid structures.

Evaluation of the resistance of DNA immobilized on ferrimagnetic particles of cobalt ferrite nanopowder against nuclease cleavage.

DNA was immobilized on ferrimagnetic particles of cobalt ferrite nanopowder (CoFe(2)O(4)) and its resistance to endonuclease (DNase I) hydrolysis was studied. Immobilization on cobalt ferrite nanoparticles prevented enzymatic cleavage of DNA. This process was not associated with enzyme inactivation under the effect of nanosize cobalt ferrite and was presumably determined by lesser availability of the DNA molecule as a result of its interaction with nanoparticles.

[Investigation of the interaction between DNA and cobalt ferrite nanoparticles by FTIR spectroscopy].

The interaction of DNA with nanoparticles of cobalt ferrite powder prepared by the mechano-chemical method was studied. It was shown that CoFe(2)O(4) nanoparticles efficiently bind DNA in aqueous solutions (Tris-HCl), forming a bionanocomposite. The adsorption capacity of CoFe(2)O(4) nanoparticles for DNA was evaluated to be 5.25 x 10(-3) mol/m(2). The desorption of DNA from the surface of the particles was analyzed while changing the pH, the ionic strength, and the chemical content of the medium. The DNA-CoFe(2)O(4) nanocomposite was investigated by FTIR spectroscopy. The block of the data allowed one to consider the mechanism of the interaction between a polynucleotide and CoFe(2)O(4) nanoparticles and to make the assumption that the binding occurred due to the coordination interaction of the phosphate groups and heterocyclic bases of DNA (oxygen atoms of thymine and guanine) with metal ions on the particle surface. The analysis of the IR spectra showed that binding can lead to the partial destabilization of the DNA structure, with the B conformation of a polynucleotide being preserved.