To get insight into attributes of propylene oxalate ring-opening polymerization catalyzed by Sn(Oct)2, the polymerization was initiated by benzyl alcohol. According to 1H NMR and MALDI-TOF mass spectrometry, the polymer chains were terminated by propylene glycol and benzyl residues, which amount correlated perfectly. The quantitative incorporation of the initiator into polyoxalates is the key to their functionalization and the synthesis of block-copolymers.

Critical micelle concentrations (CMCs) of Pluronics were determined by three techniques, namely 1,6-diphenyl-1,3,5-hexatriene fluorescence, sensitization of multidrug-resistant cancer cells with Pluronic unimers and a novel technique based on the migration of fluorophore-labeled lipid from liposomes into Pluronic micelles. The CMCs of each Pluronic determined by the three methods differ by no more than 30% and are consistent with data reported by different research teams. A literature review revealed a widely cited dataset of CMC values that differ significantly from data reported by other research groups, including ours. H O Pluronic unifier O O O n Me m n C > CMC H Whether CMC values are reliable or not? That is the question! Cellular responses

A method for sensing pectinase activity was proposed based on the formation of polyelectrolyte complexes of negatively charged, glutathione-coated, fluorescent gold nanoclusters Au22(SG)18 with the polycation 3,3-ionene and the anionic polysaccharide pectin. The formation of polyelectrolyte complexes of the nanoclusters with ionene leads to an increase in fluorescence due to the aggregation-induced emission enhancement effect, while after the addition of the natural polyanion pectin, the emission decreases. Enzymatic hydrolysis of pectin by pectinase resulted in the recovery of the fluorescence of nanoclusters, which allows sensing the activity of pectinase. 600 700 800 l/nm 600 700 800 Fluorescence intensity Fluorescence intensity 0.25 0.20 0.15 0 20 40 60 80 100 Time/min Pectinase Fluorescence intensity l/nm

The peroxyoxalate chemiluminescent reaction is an excellent source of excitation for photosensitizers used in theranostics for identification and targeting of tumor cells that produce elevated amounts of hydrogen peroxide. However, the substrates of peroxyoxalate chemiluminescent reaction, aromatic oxalates, are highly susceptible to hydrolysis in aqueous surroundings. Solubilization of oxalates in nanoreactors with a hydrophobic core significantly reduces their degradation by water. In this study, we compared for the first time the efficiency of the peroxyoxalate chemiluminescent reaction in emulsion and micellar nanoreactors. Two oxalates were studied herein, i.e. a highly active bis(2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl) oxalate (CPPO) and nearly 15-fold less active but bioinspired tyrosine-based oxalate (BTEE-ox), which differed significantly in the pKa of the leaving phenolic group, cytotoxicity, and hydrophobicity. Encapsulation of both oxalates into emulsion nanoreactors increased stability of both oxalates approximately by two orders of magnitude as compared to a THF/water (4 : 1) homogeneous solution. However, the emulsion underwent colloidal destabilization due to Ostwald ripening. In contrast, polylactide-block-poly(ethylene glycol) micelles exhibited excellent colloidal stability and ensured low rate of oxalates hydrolysis. The chemiluminescence activity of BTEE-ox solubilized in micelles became even higher than that of CPPO indicating that solid nanoreactors influenced the peroxyoxalate chemiluminescent reaction efficiency.

Ring-opening polymerization (ROP) of the six-membered cyclic propylene oxalate was studied for the first time. The reaction proceeded with a high limiting conversion of about 96 % at 100 degrees C in the presence of tin(II) octoate. Linear macromolecules, Mw of 20-30 x 10(3), D similar to 2, represented 86 % of the product, 4 % came from the equilibrium concentration of monomer, while the rest 10 % were cyclic oligomers consisting of 3-10 repeat units. ROP was accompanied by partial (about 30 %) conversion of the catalyst into the insoluble tin(II) oxalate in the course of polymer cross-linking reaction. The kinetics of polymerization obeyed first-order law, indicating typical for ROP constant number of active centers during the process. Polymerization without catalyst was 2000 times slower and also resulted in formation of polymer with D similar to 2. Addition of benzyl alcohol to the polymerization mixture resulted in its inclusion into linear macromolecules and a decrease in their molecular weight. The results point to the possibility of synthesizing propylene oxalate block copolymers using macroinitiators with hydroxyl end groups.

We synthesized a biocompatible substrate of the peroxy-oxalate chemiluminescent reaction on the basis of N-benzoyl-L-tyrosine ethyl ester. Its ability to interact with hydrogen peroxide was evaluated by light emission in the presence of a perylene activator. Its cytotoxicity is three times less than that of bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate (CPPO).

In screening, the dilution of DMSO stock solution of a lipophilic molecule with an assay medium often causes compound precipitation. To overcome the issue, the application of Pluronics as cosolvents was examined using a phenotypic sea urchin embryo assay that allows for the quick and facile evaluation of the antiproliferative effect together with systemic toxicity. Maximum tolerated concentration values for Pluronics L121, P123, and F127 were 1.4 μM, 8.6 μM, and 39.7 μM, respectively, and correlated directly with their hydrophilicity. Pluronics L121 and P123 suppressed cleavage and blastomeres retained the round shape, unlike hydrophilic Pluronic F127, which induced fertilization envelope creasing and embryo deformation that could be associated with the interaction of hydrophilic PEO units with mucopolysaccharides at the surface of sea urchin embryos. The toxicity of P123, but not of L121 and F127, was temperature-dependent and markedly increased at lower temperatures. CMC values obtained at different temperatures confirmed that the toxic effect of P123 was associated with both unimers and micelles, whereas F127 toxicity was related mainly to micelles. Evaluation using phenotypic sea urchin embryo assay revealed that potent microtubule destabilizers, namely albendazole, diarylisoxazole, and two chalcones, retained antimitotic activity after the dilution of their DMSO or 2-pyrrolidone stock solutions with 1.25% w/v Pluronic P123 or 5% w/v Pluronic F127. It was suggested that Pluronic P123 and Pluronic F127 could be used as cosolvents to improve the solubility of lipophilic molecules in aqueous medium.

To elucidate factors stirring the manifestation of different biological effects of Pluronics, we exposed multidrug resistant NCI/ADR-RES cells to various concentrations of polymers in the absence or presence of 5 mu g/mL of doxorubicin. This method of analysis showed that each Pluronic exhibits chemosensitizing, cell supporting, and cytotoxic properties depending on its concentration. The effects developed in certain concentration ranges specific to each polymer. The free energies of Pluronics interaction with the lipids of cell membrane determined from the concentration dependencies of MDR suppression were close to the free energies of Pluronics partitioning between water and lipid bilayer of liposomes, indicating that PPO-lipid interaction underlies MDR suppression. Free energies corresponding to the increase in cell viability correlated with Pluronic's binding to cells. It follows that cell support by Pluronics results from their attachment to the cell surface. The presented data are feasible for predicting the biological properties of PEG-containing block copolymers.

New procedures for the preparation of grafted and branched amphiphilic copolymers based on poly(ethylene glycol) have been suggested. Radical polymerization with TEMPO and sulfuric acid has afforded controlled synthesis of grafted copolymers of methyl methacrylate with poly(ethylene glycol) methacrylate. Radical copolymerization of allyl acetate with poly(ethylene glycol) acrylate in the presence of divinylbenzene has given branched copolymers. It has been shown that these copolymers can form micelles in aqueous medium; cytotoxicity of the copolymers and the ability to suppress the resistance of human cancer cells NCI/ADR-RES have been investigated.

This review is the first attempt to consider application of some principles of green chemistry to reversible-deactivation radical polymerization mediated by nitroxides. The results of controlled synthesis of easily degradable polymers and polymers synthesized under conditions of green chemistry by photopolymerization, polymerization in supercritical carbon dioxide, and polymerization of monomers from renewable raw materials are discussed.

Here we report formation of gold nanoparticles (GNPs) in micelles of polytyrosine-PEG copolymers that combine the properties of a reducer and a stabilizer. The size and properties of the GNPs were tailored by the excess chloroaurate over the copolymer. The latter quickly formed non-covalent complexes with HAuCl4 and then slowly reduced it to form GNPs. 3 Tyr residues are consumed by reduction of one mole of chloroaurate. The size of the GNPs was controlled by the [Tyr]/[Au(iii)] molar ratio. Small GNPs with D ≅ 8 nm were formed at [Tyr]/[Au(iii)] = 0.5-1.5. 90% of these small GNPs remained bound to the copolymer and could be stored in a lyophilized state. Such polypeptide-gold hybrid materials produced at [Tyr]/[Au(iii)] = 0.5 demonstrated high activity in the catalytic reduction of 4-nitrophenol by sodium borohydride. [Tyr]/[Au(iii)] = 5 led to the formation of large nanoplates (D ≅ 30-60 nm). Thus, in the polymer-based system the GNP size grew in line with the excess of the reducing agent in contrast to Turkevich synthesis of GNPs with citric acid, which also combines the functions of a stabilizer and a reducer. The difference results from the reduction of HAuCl4 in solution according to the Turkevich method and in the micelles of the amphiphilic polymer where the seed growth is limited by the amount of neighboring reducer.

Anionic liposomes were electrostatically adsorbed onto the surface of cationic chitosan particles cross-linked by sulfate anions, forming multi-liposomal containers (MLCs) for encapsulation and delivery of bioactive substances. An increase in molecular mass of chitosan from 30 to 300 kDa results in a size increase of chitosan particles, from 200 to 400 nm. Being saturated by liposomes, chitosan particles give MLCs of 320-540 nm. Each chitosan particle carries between 60 and 200 liposomes. The proteolytic complex Morikrase, a mixture of enzymes with various specificities, induces degradation of MLCs down to particles of size 10-15 nm; the higher the molecular mass of chitosan, the slower the enzyme-induced MLCs' degradation. pH variation within 5.5-7 and cholesterol incorporation into the liposomal membrane both have a minor effect on the rate of MLCs' biodegradation. Both the MLCs and the products of their biodegradation show low cytotoxicity. These results are of interest for constructing biodegradable capacious carriers of bioactive substances. (c) 2021 Elsevier B.V. All rights reserved.

Here, we report on the evaluation of critical packing parameters, PC, of l-tyrosine and ethylene glycol (PEG) amphiphilic block copolymers. The copolymers were synthesized via l-tyrosine-N-carboxyanhydride ring-opening polymerization using different amino-terminated PEGs as macroinitiators. The size and shape of their associates formed in water were investigated by transmission electron microscopy and dynamic and static light scatterings. The copolymers containing 20–30 wt. % of Tyr formed rod-like micelles. The copolymers with 30–50 wt. % of Tyr formed spherical vesicles, while those with 50–80 wt. % Tyr formed irregularly shaped polymeric nanoparticles. PC of the copolymers was estimated as the ratio of the van der Waals volume of the hydrophobic block (V) to its length (L) and the cross-sectional area of the polar block (SH). The values of SH for each copolymer were calculated according to the equation obtained from the correlation analysis of the published data. The hydrophobic block length L was calculated in three ways, i.e., assuming that polytyrosine adopts (1) stretched, (2) amyloid hairpin, or (3) Gaussian coil conformation. In the latter case, the best match of the calculated PC values with the morphology of the copolymer assemblies was observed.

Stimulus-sensitive liposomes have been prepared from zwitterionic dioleoylphosphocholine and ampholytic molecular switches with carboxylic anionic groups and the triazole or isobutylamino cationic ones attached to the opposite ends of the steroid core. When the pH of outer solution was altered from slightly alkaline to slightly acidic, the switches changed their orientation in the liposomal membrane, which induced temporal defects formation and the release of a drug model load. The low-toxic pH-sensitive isobutylamino derivative–dioleoylphosphocholine liposomes demonstrated fast cargo release.

Positively charged linear chitosan molecules were cross-linked with sulfate-anions to form chitosan nano-particles which were used as a scaffold of negatively charged cardiolipin/egg lecithin liposomes loaded with doxorubicin (DOX). Thus formed multi-liposomal complexes (MLCs) containing 55 liposomes/chitosan and bearing a slight positive net charge effectively transmitted DOX into the cytoplasm of cells in culture. The efficiency of DOX delivery increased 4-5-fold upon drug incorporation in MLCs. Inside the cells, the penetrated MLCs released DOX thus enabling its accumulation in the nuclei and interaction with its intracellular target DNA leading to a decrease in cell survival. The effects were demonstrated on 3T3 line of mouse fibroblasts, drug sensitive tumor MCF-7 cells and drug resistant human ovarian carcinoma OVCAR-8 cells (formerly called MCF-7/ADR). Thus, MLC particles can be used for effective delivery of payloads in cells of different origin.

A new synthesis of poly(methyl methacrylate) vinyl-terminated macromonomer is performed using the disproportionation between propagating methyl methacrylate radical and nitroxide TEMPO. The ability of the macromonomer to polymerize and copolymerize with styrene and poly(ethylene glycol) methacrylate was confirmed by GPC and isothermal calorimetry.

A novel strategy is described for preparing pH-sensitive liposomes which releases the encapsulated drug in response to the change in pH of surrounding solution. The liposomes, composed of conventional zwitter-ionic egg yolk lecithin (EL), additionally contains a pH-sensitive "activator" (AMS), a derivative of lithocholic acid with anionic and cationic groups attached to the opposite ends of the steroid core. AMS changes its orientation in the liposomal membrane thus adapting to acidity/basicity of the outer solution. The rotation of AMS induces disordering of the membrane and a fast release of the bioactive cargo. In particular, 50-60 % of the encapsulated antitumor drug, doxorubicin and cisplatin, leaks from the liposomes within the first minute after acidification of the surrounding solution. Low-toxic EL-AMS liposomes, loaded with doxorubicin, show themselves active towards multidrug resistant cells. Fast-acting and low-toxic EL-AMS liposomes can be used in the design of smart liposomal containers in the drug delivery field.

Many natural substances exhibit anti-inflammatory activity and considerable potential in prophylaxis and treatment of allergies. Knowing exact molecular targets, which is required for developing these as medicinal products, is often challenging for multicomponent compositions. In the present study we examined novel polyphenolic substance, a water-soluble fraction of wood lignin (laboratory code BP-Cx-1). In our previous study, a number of polyphenolic components of BP-Cx-1 (flavonoids, sapogenins, phenanthrenes etc.) were identified as the major carriers of biological activity of BP-Cx drug family, and several molecular targets involved in cancer and/or inflammation signaling pathways were proposed based on the results of the in vitro and in silico screening studies. In the present study, half maximal inhibitory concentration (IC50) of BP-Cx-1 was established with a radio-ligand method and a range of IC50 values between 22.8 and 40.3 mu g/ml were obtained for adenosine receptors A1, A2A and prostaglandin receptors EP2, IP (PGI2). IC50 for serotonin 5-HT1 and for glucocorticoid GR receptors were 3.0 mu g/ml and 12.6 mu g/ml, respectively, both being within the range of BP-Cx-1 concentrations achievable in in vivo models. Further, distribution of [H-3] labelled BP-Cx-1 in NIH3T3 murine fibroblasts and MCF7/R carcinoma cells was studied with autoradiography. [H-3]-BP-Cx-1 (visualized as silver grains produced by tritium beta particles) was mainly localized along the cell membrane, in the perinuclear region and in the nucleus, suggesting ability of BP-Cx-1 to enter cells and bind to membrane or cytosol receptors. In our experiment, we observed the effect of BP-Cx-1 on maturation of dendritic cells (DCs): downregulation of expression of the lipid-presentation molecule CD1a, co-stimulatory molecules CD80, CD83 and CD 40, decreased production of pro-inflammatory cytokines IL-4 and TNF-alpha and increased production of anti-inflammatory cytokine IL-10. It is hypothesized that [H-3]-BP-Cx-1 detectable in the nucleus is part of the activated GR complex, known to be involved in regulation of transcription of genes responsible for the anti-inflammatory response. Based on IC50, cell distribution data and results of the experiment with DCs it is suggested that the in vivo effects of BP-Cx-1 are mediated via GR and 5-HT1 receptors thus promoting development of tolerogenic effector function in dendritic cells.