Polymer particles containing Fe-based metalloporphyrin as a highly efficient stimulator of reactive oxygen species formation in vitro and in vivo

Russian Chemical Bulletin - Reactive oxygen species are generated by the redox reaction involving metalloporphyrin and ascorbic acid (AA) and lead to oxidative stress followed by cancer cell death....     

Synthesis and study of the composition and properties of chelate complexes of benzoyl acetonates of rare-earth elements and use of these in gas chromatography

Chelate complex cerium [Ce(BA)₃)] and europium [Eu(BA)₃] benzoyl acetonates were synthesized. According to IR spectroscopic data and elemental analyses, the composition of the complexes is described by the empirical formulas M(BA)₃·2H₂O. Sorbents based on a mesoporous silica gel modified with cerium and europium benzoyl acetonates were obtained. The nitrogen porosimetry demonstrated that, as the complexes are deposited onto the surface of the starting support, the specific surface area and the pore volume become smaller. The polarity of the sorbents Chromaton N-AW + SiO₂ + M(BA)₃ with respect to all classes of test compounds decreases in the order Ce^III > Eu^III. According to the data obtained for the capacity factors, the sorbent modified with cerium benzoyl acetonate selectively separates alcohols, and Chromaton N-AW + SiO₂ with deposited chelates Eu(BA)₃ shows the best separating capacity for alkanes and alcohols. It was shown that the sorbents can be used in practice for separating gaseous mixtures of light hydrocarbons.     

Polymer nanoparticles loaded with FeCl-tetraphenylporphyrin for binary catalytic therapy of neoplasms

Russian Chemical Bulletin - In order to study the possibility of using a metal complex of the porphyrin series, FeIIICl-tetraphenylporphyrin (FeClTPP), and its polymeric form as antitumor agents...     

Development of a polymer system for the delivery of daunorubicin to tumor cells to overcome drug resistance

Method for the synthesis of polymeric nanoparticles (NP) with encapsulated daunorubicin (DNR) was developed on the basis of double emulsion solvent evaporation technique using biodegradable poly(lactide-co-glycolide) (PLGA), which is aimed at customization of pharmacokinetic properties of the preparation, enhanced accumulation of DNR in tumor cells and prolongation of its action. The obtained polymer nanoparticles (DNR-PLGA) had average size ranging around 138±36 nm, with zeta-potential of –25.3 mV and the polydispersity index (PDI) of 0.072. The release kinetics of DNR from polymer nanoparticles at pH 7.4 and 5.0 has been studied. In vitro studies showed similar specific activity of DNR- PLGA in K562 and MCF-7 cancer cell lines together with an increase in activity in K562 Adr and MCF-7 Adr cell lines, which are anthracycline resistant, by 1.6 and 3.4 times. The study demonstrated the efficacy of the developed PLGA-based DNR delivery system in the improvement of antitumor effect of DNR, overcoming multidrug resistance in cancer cells, and also in the decrease in nonspecific toxicity of the preparation.     

Influence of chloride ions,pH and humic substances on complexation of cadmium(II) and copper(II)

An influence of chloride ions, pH and humic substances concentration on complexation of cadmium(II)and copper(II) ions with humic acids was studied by means of inversion-voltamperometry using the method of experimental design. Equations establishing dependences of concentrations of humate complexes of cadmium(II) and copper(II) on concentrations of chloride and humic substances and pH values too were derived.     

Cellular internalization of targeted and non-targeted delivery systems for contrast agents based on polyamidoamine dendrimers

New high-molecular-weight contrast agents based on polyamidoamine (PAMAM) dendrimers for targeted imaging of malignant tumors characterized by overexpression of human epidermal growth factor receptor (EGFR) and human alpha-fetoprotein receptor (RECAF) were designed. Conjugates of second (G2) and third (G3) generation polyamidoamine dendrimers with 1,4,7,10-tetraazocyclodecane-1,4,7,10-tetraacetic acid (DOTA) were obtained. The quantitative composition of the conjugates was determined by ¹HNMR spectroscopy. It was shown that four out of the 16 terminal NH₂ groups in G2-DOTA and nine out of the 32 groups in G3-DOTA were modified with DOTA. The morphology, size, and charge of the synthesized macromolecules were characterized by dynamic light scattering and electrophoresis. Gadolinium(III) was loaded into the conjugates and the Gd content was determined by atomic emission spectroscopy. For increasing the selectivity of accumulation in the tumor cells, two recombinant proteins able to bind selectively to EGFR and RECAF, namely, human recombinant epidermal growth factor (rEGF) and human recombinant 3rd domain of alpha-fetoprotein (3dAFPpG), were conjugated with G2 and G3 dendrimers. The conjugates containing vector molecules were mainly accumulated via clathrin-dependent endocytosis, whereas G2-DOTA and G3-DOTA were absorbed via caveolin-dependent endocytosis and macropinocytosis. The dendrimer conjugates with vector molecules were intensely accumulated in A549 cells characterized by high expression of EGFR (Herl) and RECAF, whereas the accumulation of conjugates in the control K562 cells (with low expression of Her1) and in the CD14^? population of human unstimulated mononuclear white blood cells was insignificant. The 3dAFPpG-conjugated dendrimers were partly recycled. All synthesized conjugates had a rather low toxicity in the range of 350–450 µmol L^?1 (IC₅₀).

     

Chromatographic properties of mesoporous silica gel modified with acetylacetonates of europium and copper

New mesoporous materials prepared from tetraethoxysilane, i.e., sorbents obtained with the use of surfactants, are synthesized. Their chromatographic polarity is assessed quantitatively. Their Kovats retention indices and Rohrschneider polarity coefficients are calculated. Based on physicohemical data, it is demonstrated that modifying supports with metal chelates changes the structure and properties of the initial sorbents: the differential molar Gibbs free energies rise considerably for sorbent modified with copper acetylacetonate with respect to ethanol (?ΔG′ _i = 7.09 kJ/mol) and nitromethane (?ΔG′ _i = 6.75 kJ/mol), relative to the initial silica gel (5.43 and 4.15 kJ/mol, respectively).