Anionically Functionalized Glycogen Encapsulates Melittin by Multivalent Interaction.

We developed acid-functionalized glycogen conjugates as supramolecular carriers for efficient encapsulation and inhibition of a model cationic peptide melittin─the main component of honeybee venom. For this purpose, we synthesized and characterized a set of glycogens, functionalized to various degrees by several different acid groups. These conjugates encapsulate melittin up to a certain threshold amount, beyond which they precipitate. Computer simulations showed that sufficiently functionalized conjugates electrostatically attract melittin, resulting in its efficient encapsulation in a broad pH range around the physiological pH. Hemolytic assays confirmed in vitro that the effective inhibition of melittin's hemolytic activity occurs for highly functionalized samples, whereas no inhibition is observed when using low-functionalized conjugates. It can be concluded that functional glycogens are promising carriers for cationic molecular cargos or antidotes against animal venoms under conditions, in which suitable properties such as biodegradability and biocompatibility are crucial.

Thermo- and ROS-Responsive Self-Assembled Polymer Nanoparticle Tracers for 19F MRI Theranostics.

Fluorine-19 magnetic resonance imaging (19F MRI) enables detailed in vivo tracking of fluorine-containing tracers and is therefore becoming a particularly useful tool in noninvasive medical imaging. In previous studies, we introduced biocompatible polymers based on the hydrophilic monomer N-(2-hydroxypropyl)methacrylamide (HPMA) and the thermoresponsive monomer N-(2,2-difluoroethyl)acrylamide (DFEA). These polymers have abundant magnetically equivalent fluorine atoms and advantageous properties as 19F MRI tracers. Furthermore, in this pilot study, we modified these polymers by introducing a redox-responsive monomer. As a result, our polymers changed their physicochemical properties once exposed to an oxidative environment. Reactive oxygen species (ROS)-responsive polymers were prepared by incorporating small amounts (0.9-4.5 mol %) of the N-[2-(ferrocenylcarboxamido)ethyl]acrylamide (FcCEA) monomer, which is hydrophobic and diamagnetic in the reduced electroneutral (Fe(II), ferrocene) state but hydrophilic and paramagnetic in the oxidized (Fe(III), ferrocenium cation) state. This property can be useful for theranostic purposes (therapy and diagnostic purposes), especially, in terms of ROS-responsive drug-delivery systems. In the reduced state, these nanoparticles remain self-assembled with the encapsulated drug but release the drug upon oxidation in ROS-rich tumors or inflamed tissues.

Internal Nanoparticle Structure of Temperature-Responsive Self-Assembled PNIPAM-b-PEG-b-PNIPAM Triblock Copolymers in Aqueous Solutions: NMR, SANS, and Light Scattering Studies.

In this study, we report detailed information on the internal structure of PNIPAM-b-PEG-b-PNIPAM nanoparticles formed from self-assembly in aqueous solutions upon increase in temperature. NMR spectroscopy, light scattering, and small-angle neutron scattering (SANS) were used to monitor different stages of nanoparticle formation as a function of temperature, providing insight into the fundamental processes involved. The presence of PEG in a copolymer structure significantly affects the formation of nanoparticles, making their transition to occur over a broader temperature range. The crucial parameter that controls the transition is the ratio of PEG/PNIPAM. For pure PNIPAM, the transition is sharp; the higher the PEG/PNIPAM ratio results in a broader transition. This behavior is explained by different mechanisms of PNIPAM block incorporation during nanoparticle formation at different PEG/PNIPAM ratios. Contrast variation experiments using SANS show that the structure of nanoparticles above cloud point temperatures for PNIPAM-b-PEG-b-PNIPAM copolymers is drastically different from the structure of PNIPAM mesoglobules. In contrast with pure PNIPAM mesoglobules, where solidlike particles and chain network with a mesh size of 1-3 nm are present, nanoparticles formed from PNIPAM-b-PEG-b-PNIPAM copolymers have nonuniform structure with "frozen" areas interconnected by single chains in Gaussian conformation. SANS data with deuterated "invisible" PEG blocks imply that PEG is uniformly distributed inside of a nanoparticle. It is kinetically flexible PEG blocks which affect the nanoparticle formation by prevention of PNIPAM microphase separation.

Thermodynamics of the multi-stage self-assembly of pH-sensitive gradient copolymers in aqueous solutions.

The self-assembly thermodynamics of pH-sensitive di-block and tri-block gradient copolymers of acrylic acid and styrene was studied for the first time using isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) performed at varying pH. We were able to monitor each step of micellization as a function of decreasing pH. The growth of micelles is a multi-stage process that is pH dependent with several exothermic and endothermic components. The first step of protonation of the acrylic acid monomer units was accompanied mainly by conformational changes and the beginning of self-assembly. In the second stage of self-assembly, the micelles become larger and the number of micelles becomes smaller. While solution acidity increases, the isothermal calorimetry data show a broad deep minimum corresponding to an exothermic process attributed to an increase in the size of hydrophobic domains and an increase in the structure's hydrophobicity. The minor change in heat capacity (ΔCp) confirms the structural changes during this exothermic process. The exothermic process terminates deionization of acrylic acid. The pH-dependence of the ζ-potential of the block gradient copolymer micelles exhibits a plateau in the regime corresponding to the pH-controlled variation of the micellar dimensions. The onset of micelle formation and the solubility of the gradient copolymers were found to be dependent on the length of the gradient block.

Smart Poly(lactide)-b-poly(triethylene glycol methyl ether methacrylate) (PLA-b-PTEGMA) Block Copolymers: One-Pot Synthesis, Temperature Behavior, and Controlled Release of Paclitaxel.

This paper introduces a new class of amphiphilic block copolymers created by combining two polymers: polylactic acid (PLA), a biocompatible and biodegradable hydrophobic polyester used for cargo encapsulation, and a hydrophilic polymer composed of oligo ethylene glycol chains (triethylene glycol methyl ether methacrylate, TEGMA), which provides stability and repellent properties with added thermo-responsiveness. The PLA-b-PTEGMA block copolymers were synthesized using ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization (ROP-RAFT), resulting in varying ratios between the hydrophobic and hydrophilic blocks. Standard techniques, such as size exclusion chromatography (SEC) and 1H NMR spectroscopy, were used to characterize the block copolymers, while 1H NMR spectroscopy, 2D nuclear Overhauser effect spectroscopy (NOESY), and dynamic light scattering (DLS) were used to analyze the effect of the hydrophobic PLA block on the LCST of the PTEGMA block in aqueous solutions. The results show that the LCST values for the block copolymers decreased with increasing PLA content in the copolymer. The selected block copolymer presented LCST transitions at physiologically relevant temperatures, making it suitable for manufacturing nanoparticles (NPs) and drug encapsulation-release of the chemotherapeutic paclitaxel (PTX) via temperature-triggered drug release mechanism. The drug release profile was found to be temperature-dependent, with PTX release being sustained at all tested conditions, but substantially accelerated at 37 and 40 °C compared to 25 °C. The NPs were stable under simulated physiological conditions. These findings demonstrate that the addition of hydrophobic monomers, such as PLA, can tune the LCST temperatures of thermo-responsive polymers, and that PLA-b-PTEGMA copolymers have great potential for use in drug and gene delivery systems via temperature-triggered drug release mechanisms in biomedicine applications.

A New Method to Prepare Stable Polyaniline Dispersions for Highly Loaded Cathodes of All-Polymer Li-Ion Batteries.

A new method for the preparation of polyaniline (PANI) films that have a 2D structure and can record high active mass loading (up to 30 mg cm-2) via acid-assisted polymerization in the presence of concentrated formic acid was developed. This new approach represents a simple reaction pathway that proceeds quickly at room temperature in quantitative isolated yield with the absence of any byproducts and leads to the formation of a stable suspension that can be stored for a prolonged time without sedimentation. The observed stability was explained by two factors: (a) the small size of the obtained rod-like particles (50 nm) and (b) the change of the surface of colloidal PANI particles to a positively charged form by protonation with concentrated formic acid. The films cast from the concentrated suspension were composed of amorphous PANI chains assembled into 2D structures with nanofibrillar morphology. Such PANI films demonstrated fast and efficient diffusion of the ions in liquid electrolyte and showed a pair of revisable oxidation and reduction peaks in cyclic voltammetry. Furthermore, owing to the high mass loading, specific morphology, and porosity, the synthesized polyaniline film was impregnated by a single-ion conducting polyelectrolyte-poly(LiMn-r-PEGMm) and characterized as a novel lightweight all-polymeric cathode material for solid-state Li batteries by cyclic voltammetry and electrochemical impedance spectroscopy techniques.

Plasmonic Ag/Cu/PEG nanofluids prepared when solids meet liquids in the gas phase.

Since the time of Faraday's experiments, the optical response of plasmonic nanofluids has been tailored by the shape, size, concentration, and material of nanoparticles (NPs), or by mixing different types of NPs. To date, water-based liquids have been the most extensively investigated host media, while polymers, such as poly(ethylene glycol) (PEG), have frequently been added to introduce repulsive steric interactions and protect NPs from agglomeration. Here, we introduce an inverse system of non-aqueous nanofluids, in which Ag and Cu NPs are dispersed in PEG (400 g mol-1), with no solvents or chemicals involved. Our single-step approach comprises the synthesis of metal NPs in the gas phase using sputtering-based gas aggregation cluster sources, gas flow transport of NPs, and their deposition (optionally simultaneous) on the PEG surface. Using computational fluid dynamics simulations, we show that NPs diffuse into PEG at an average velocity of the diffusion front of the order of µm s-1, which is sufficient for efficient loading of the entire polymer bulk. We synthesize yellow Ag/PEG, green Cu/PEG, and blue Ag/Cu/PEG nanofluids, in which the color is given by the position of the plasmon resonance. NPs are prone to partial agglomeration and sedimentation, with a slower kinetics for Cu. Density functional theory calculations combined with UV-vis data and zeta-potential measurements prove that the surface oxidation to Cu2O and stronger electrostatic repulsion are responsible for the higher stability of Cu NPs. Adopting the De Gennes formalism, we estimate that PEG molecules adsorb on the NP surface in mushroom coordination, with the thickness of the adsorbed layer L < 1.4 nm, grafting density σ < 0.20, and the average distance between the grafted chains D > 0.8 nm. Such values provide sufficient steric barriers to retard, but not completely prevent, agglomeration. Overall, our approach offers an excellent platform for fundamental research on non-aqueous nanofluids, with metal-polymer and metal-metal interactions unperturbed by the presence of solvents or chemical residues.

Potentiometric Performance of Ion-Selective Electrodes Based on Polyaniline and Chelating Agents: Detection of Fe2+ or Fe3+ Ions.

We constructed a sensor for the determination of Fe2+ and/or Fe3+ ions that consists of a polyaniline layer as an ion-to-electron transducer; on top of it, chelating molecules are deposited (which can selectively chelate specific ions) and protected with a non-biofouling poly(2-methyl-2-oxazoline)s layer. We have shown that our potentiometric sensing layers show a rapid response to the presence of Fe2+ or Fe3+ ions, do not experience interference with other ions (such as Cu2+), and work in a biological environment in the presence of bovine serum albumin (as a model serum protein). The sensing layers detect iron ions in the concentration range from 5 nM to 50 µM.

Temoporfin-loaded 1-tetradecanol-based thermoresponsive solid lipid nanoparticles for photodynamic therapy.

We developed fully biodegradable/metabolizable nanosystem based on polymer surfactant-stabilized thermoresponsive solid lipid nanoparticles with non-covalently bound photosensitizer temoporfin (T-SLNP) with particle size below 50nm. The efficacy of T-SLNP was compared with commercial temoporfin formulation in terms of in vitro phototoxicity in 4T1 (murine mammary carcinoma) and MDA-MB-231(human breast adenocarcinoma) cells and of in vivo anticancer effect in Nu/Nu mice bearing MDA-MB-231 tumors. In vitro study demonstrated faster accumulation kinetics in the cells for our formulation design resulting in higher phototoxicity against the tumor cells. In vivo anticancer efficacy was markedly improved by T-SLNP compared with commercial temoporfin formulation. Owing to controlled and sustained release properties, subcellular size, biocompatibility with tissue and cells, the T-SLNP nanodispersion prepared in this study represents promising drug delivery system applicable in cancer treatment.

Thermoresponsive polymer system based on poly(N-vinylcaprolactam) intended for local radiotherapy applications.

Brachytherapy represents effective local therapy of unresectable solid tumors with very few side effects. Radiolabeled thermoresponsive polymers offer almost noninvasive approach to brachytherapy applications. A radioiodinated, water-soluble, thermosensitive poly(N-vinylcaprolactam) (PVCL) polymer was prepared using two approaches. The direct copolymerization with N-methacryloyl-l-tyrosinamide, as well as end-capping of carboxy-terminated PVCL homopolymer with tyramine, were used. In both cases the product was successfully radiolabeled with (125)I. The obtained polymers demonstrate cloud-point temperature (TC) values in the range of 33-35°C in all the studied solvent systems (water, PBS (pH 7.4) and physiological saline solution). Above the cloud point temperature, the molecularly dissolved polymer is macroprecipitated from the solution. The TC values close to the human body temperature of this biocompatible poly(N-vinylcaprolactam) polymer makes it a promising material intended for local therapy of solid tumors.