Poly(2-(dimethylamino)ethyl methacrylate)-Grafted Amphiphilic Block Copolymer Micelles Co-Loaded with Quercetin and DNA.

The synergistic effect of drug and gene delivery is expected to significantly improve cancer therapy. However, it is still challenging to design suitable nanocarriers that are able to load simultaneously anticancer drugs and nucleic acids due to their different physico-chemical properties. In the present work, an amphiphilic block copolymer comprising a biocompatible poly(ethylene glycol) (PEG) block and a multi-alkyne-functional biodegradable polycarbonate (PC) block was modified with a number of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) side chains applying the highly efficient azide-alkyne "click" chemistry reaction. The resulting cationic amphiphilic copolymer with block and graft architecture (MPEG-b-(PC-g-PDMAEMA)) self-associated in aqueous media into nanosized micelles which were loaded with the antioxidant, anti-inflammatory, and anticancer drug quercetin. The drug-loaded nanoparticles were further used to form micelleplexes in aqueous media through electrostatic interactions with DNA. The obtained nanoaggregates-empty and drug-loaded micelles as well as the micelleplexes intended for simultaneous DNA and drug codelivery-were physico-chemically characterized. Additionally, initial in vitro evaluations were performed, indicating the potential application of the novel polymer nanocarriers as drug delivery systems.

Green Synthesis and the Evaluation of a Functional Amphiphilic Block Copolymer as a Micellar Curcumin Delivery System.

Polymer micelles represent one of the most attractive drug delivery systems due to their design flexibility based on a variety of macromolecular synthetic methods. The environmentally safe chemistry in which the use or generation of hazardous materials is minimized has an increasing impact on polymer-based drug delivery nanosystems. In this work, a solvent-free green synthetic procedure was applied for the preparation of an amphiphilic diblock copolymer consisting of biodegradable hydrophobic poly(acetylene-functional carbonate) and biocompatible hydrophilic polyethylene glycol (PEG) blocks. The cyclic functional carbonate monomer 5-methyl-5-propargyloxycarbonyl-1,3-dioxane-2-one (MPC) was polymerized in bulk using methoxy PEG-5K as a macroinitiator by applying the metal-free organocatalyzed controlled ring-opening polymerization at a relatively low temperature of 60 °C. The functional amphiphilic block copolymer self-associated in aqueous media into stable micelles with an average diameter of 44 nm. The copolymer micelles were physico-chemically characterized and loaded with the plant-derived anticancer drug curcumin. Preliminary in vitro evaluations indicate that the functional copolymer micelles are non-toxic and promising candidates for further investigation as nanocarriers for biomedical applications.

Correction: Grancharov et al. Flexible Polymer-Organic Solar Cells Based on P3HT:PCBM Bulk Heterojunction Active Layer Constructed under Environmental Conditions. Molecules 2021, 26, 6890.

The authors would like to correct a mistake in Figure 3 as published in the original publication [...].

Functional Polyion Complex Micelles for Potential Targeted Hydrophobic Drug Delivery.

Polyion complex (PIC) micelles have gained an increasing interest, mainly as promising nano-vehicles for the delivery of various hydrophilic charged (macro)molecules such as DNA or drugs to the body. The aim of the present study is to construct novel functional PIC micelles bearing cell targeting ligands on the surface and to evaluate the possibility of a hydrophobic drug encapsulation. Initially, a pair of functional oppositely charged peptide-based hybrid diblock copolymers were synthesized and characterized. The copolymers spontaneously co-assembled in water into nanosized PIC micelles comprising a core of a polyelectrolyte complex between poly(L-aspartic acid) and poly(L-lysine) and a biocompatible mixed shell of disaccharide-modified poly(ethylene glycol) and poly(2-hydroxyethyl methacrylate). Depending on the molar ratio between the oppositely charged groups, PIC micelles varying in surface charge were obtained and loaded with the natural hydrophobic drug curcumin. PIC micelles' drug loading efficiency, in vitro drug release profiles and antioxidant activity were evaluated. The preliminary results indicate that PIC micelles can be successfully used as carriers of hydrophobic drugs, thus expanding their potential application in nanomedicine.

Functional Polyglycidol-Based Block Copolymers for DNA Complexation.

Gene therapy is an attractive therapeutic method for the treatment of genetic disorders for which the efficient delivery of nucleic acids into a target cell is critical. The present study is aimed at evaluating the potential of copolymers based on linear polyglycidol to act as carriers of nucleic acids. Functional copolymers with linear polyglycidol as a non-ionic hydrophilic block and a second block bearing amine hydrochloride pendant groups were prepared using previously synthesized poly(allyl glycidyl ether)-b-polyglycidol block copolymers as precursors. The amine functionalities were introduced via highly efficient radical addition of 2-aminoethanethiol hydrochloride to the alkene side groups. The modified copolymers formed loose aggregates with strongly positive surface charge in aqueous media, stabilized by the presence of dodecyl residues at the end of the copolymer structures and the hydrogen-bonding interactions in polyglycidol segments. The copolymer aggregates were able to condense DNA into stable and compact nanosized polyplex particles through electrostatic interactions. The copolymers and the corresponding polyplexes showed low to moderate cytotoxicity on a panel of human cancer cell lines. The cell internalization evaluation demonstrated the capability of the polyplexes to successfully deliver DNA into the cancer cells.

Flexible Polymer-Organic Solar Cells Based on P3HT:PCBM Bulk Heterojunction Active Layer Constructed under Environmental Conditions.

In this study, some crucial parameters were determined of flexible polymer-organic solar cells prepared from an active layer blend of poly(3-hexylthiophene) (P3HT) and the fullerene derivative [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) mixed in 1:1 mass ratio and deposited from chlorobenzene solution by spin-coating on poly(ethylene terephthalate) (PET)/ITO substrates. Additionally, the positive effect of an electron transport layer (ETL) prepared from zinc oxide nanoparticles (ZnO np) on flexible photovoltaic elements' performance and stability was investigated. Test devices with above normal architecture and silver back electrodes deposed by magnetron sputtering were constructed under environmental conditions. They were characterized by current-voltage (I-V) measurements, quantum efficiency, impedance spectroscopy, surface morphology, and time-degradation experiments. The control over morphology of active layer thin film was achieved by post-deposition thermal treatment at temperatures of 110-120 °C, which led to optimization of device morphology and electrical parameters. The impedance spectroscopy results of flexible photovoltaic elements were fitted using two R||CPE circuits in series. Polymer-organic solar cells prepared on plastic substrates showed comparable current-voltage characteristics and structural properties but need further device stability improvement according to traditionally constructed cells on glass substrates.

Modification of the adhesive properties of silicone-based coatings by block copolymers.

The improvement of the (bio)adhesive properties of elastomeric polydimethylsiloxane (PDMS) coatings is reported. This is achieved by a surface modification consisting of the incorporation of block copolymers containing a PDMS block and a poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) block in a PDMS matrix, followed by matrix cross-linking and immersion of the obtained materials in water. Contact angle measurements (CA), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM) showed the presence of the PDMAEMA block at the surface, drastic morphology changes, and improved adhesion properties after immersion in water. Finally, underwater bioadhesion tests show that mussels adhere only to block copolymer-filled coatings and after immersion in water, i.e., when the PDMAEMA blocks have been brought to the coating surface. These observations highlight the significant role of hydrophilic groups in the surface modification of silicone coatings.

Polycarbonate-Based Copolymer Micelles as Biodegradable Carriers of Anticancer Podophyllotoxin or Juniper Extracts.

Podophyllotoxin (PPT) is used in the industrial production of efficient anticancer, antiviral and other drugs. Sinopodophyllum hexandrum or Podophyllum peltatum are natural sources of PPT, but at present they are considered as endangered species. Their PPT content is variable, depending on the growing conditions. Searching for new sources of PPT, some representatives of the genus Juniperus were found to exhibit efficient PPT biosynthesis. However, PPT is highly toxic and poorly soluble in water compound, which limits its clinical applications. In this connection, amphiphilic polymer micelles are considered to be suitable PPT carriers, aimed at increase in water solubility and decrease in toxicity. The present research deals with the evaluation of MPEG-polycarbonate block copolymer micelles loaded with PPT or juniper extracts. The active component-loaded polymer nanocarriers were characterized by dynamic and electrophoretic light scattering, as well as by transmission electron microscopy. The active component loading efficiency and loading capacity were also determined. Highly efficient antiproliferative activity of the loaded micelles was determined in a panel of cancer cell lines. The obtained amphiphilic nanocarriers, loaded with PPT-containing bioactive components, have application in future in vivo preclinical trials of their pharmacokinetics and pharmacodynamics as potential therapeutical agents in the prospective nanomedicine.

Solvent-Free Synthesis of Multifunctional Block Copolymer and Formation of DNA and Drug Nanocarriers.

The synthesis of well-defined multifunctional polymers is of great importance for the development of complex materials for biomedical applications. In the current work, novel and multi-amino-functional diblock copolymer for potential gene and drug delivery applications was successfully synthesized. A highly efficient one-step and quantitative modification of an alkyne-functional polycarbonate-based precursor was performed, yielding double hydrophilic block copolymer with densely grafted primary amine side groups. The obtained positively charged block copolymer co-associated with DNA, forming stable and biocompatible nanosized polyplexes. Furthermore, polyion complex (PIC) micelles with tunable surface charge and decorated with cell targeting moieties were obtained as a result of direct mixing in aqueous media of the multi-amino-functional block copolymer and a previously synthesized oppositely charged block copolymer bearing disaccharide end-group. The obtained well-defined nanosized PIC-micelles were loaded with the hydrophobic drug curcumin. Both types of nanoaggregates (polyplexes and PIC-micelles) were physico-chemically characterized. Moreover, initial in vitro evaluations were performed to assess the nanocarriers' potential for biomedical applications.

Flexible Polymer-Ionic Liquid Films for Supercapacitor Applications.

Mechanically and thermally stable novel gel polymer electrolytes (GPEs) have been prepared and applied in supercapacitor cells. Quasi-solid and flexible films were prepared by solution casting technique and formulated by immobilization of ionic liquids (ILs) differing in their aggregate state. A crosslinking agent and a radical initiator were added to further stabilize them. The physicochemical characteristics of the obtained crosslinked films show that the realized cross-linked structure contributes to their improved mechanical and thermal stability, as well as an order of magnitude higher conductivity than that of the non-crosslinked ones. The obtained GPEs were electrochemically tested as separator in symmetric and hybrid supercapacitor cells and showed good and stable performance in the investigated systems. The crosslinked film is suitable for use as both separator and electrolyte and is promising for the development of high-temperature solid-state supercapacitors with improved capacitance characteristics.

Biorenewable Oxypropylated Pentane-1,2,5-triol as a Source for Incorporation in Rigid Polyurethane Foams.

In this study, as a product from the efficient Achmatowicz rearrangement and mild subsequent hydrogenation-reduction reactions of biorenewable C5 alcohols derived from lignocellulose, pentane-1,2,5-triol was successfully used after oxypropylation in the preparation of rigid polyurethane foams-one of the most important classes of polymeric materials. Despite the broad range of applications, the production of polyurethanes is still highly dependent on petrochemical materials considering the need of renewable raw materials and new process technologies for the production of polyol or isocyanate components as a key point for the sustainable development of polyurethane foams. The synthesized oxypropylated pentane-1,2,5-triol was analyzed using proton NMR spectroscopy, hydroxyl number, and viscosity, whereas the newly obtained foams incorporated with up to 30% biorenewable polyol were characterized using compressive stress, thermogravimetry, dynamic mechanical analysis, and scanning electron microscopy. The modified rigid polyurethanes showed better compressive strength (>400.0 kPa), a comparable thermal degradation range at 325-450 °C, and similar morphological properties to those of commercial polyurethane formulations.

Triblock Copolymer Micelles with Tunable Surface Charge as Drug Nanocarriers: Synthesis and Physico-Chemical Characterization.

Polymeric micelles have gained increasing interest as efficient drug delivery systems for cancer treatment and diagnosis. The aim of the present study was to construct and to evaluate novel polymeric nanosized drug carriers with tunable surface charges. Initially, amphiphilic triblock copolymers with predetermined molar mass characteristics were synthesized by applying controlled polymerization techniques. The copolymers self-assembled in aqueous media into core-shell spherical micelles, comprising a biodegradable hydrophobic poly(D,L-lactide) core, positively charged middle layer of poly((2-dimethylamino)ethyl methacrylate), and an outer shell of neutral hydrophilic poly(oligo(ethylene glycol) methyl ether methacrylate), with various densities of the short polyether side chains. The block copolymer micelles with average diameters of about 70 nm and surface charges varying from strongly positive to neutral were characterized and loaded with the model, natural, hydrophobic drug curcumin. Characteristics such as drug loading efficiency, in-vitro drug release profiles, and stability under physiological conditions were evaluated and discussed in terms of nanocarriers' composition. As a result, the most promising candidates for potential application in nanomedicine were identified.

Nanoarchitectonics of Spherical Nucleic Acids with Biodegradable Polymer Cores: Synthesis and Evaluation.

Spherical nucleic acids (SNAs) have gained significant attention due to their unique properties allowing them to overcome the challenges that face current nanocarriers used for gene therapies. The aim of this study is to synthesize and characterize polymer-oligonucleotide conjugates of different architecture and to evaluate the possibility of forming SNAs with biodegradable cores. Initially, two types of azide (multi)functional polyester-based (co)polymers were successfully synthesized and characterized. In the next step, short oligonucleotide strands were attached to the polymer chains applying the highly efficient and metal-free "click" reaction, thus forming conjugates with block or graft architecture. Both conjugates spontaneously self-assembled in aqueous media forming nanosized SNAs with a biodegradable polyester core and a surface of oligonucleotide chains as evidenced from dynamic and electrophoretic light scattering measurements. The nano-assemblies were in vitro evaluated for potential cytotoxicity. Furthermore, the interactions of the newly synthesized SNAs with membrane lipids were studied. The preliminary results indicate that both types of polymer-based SNAs are good candidates for potential application in gene therapy and that it is worth to be further evaluated.

Multifunctional Polymer Nanocarrier for Efficient Targeted Cellular and Subcellular Anticancer Drug Delivery.

A multifunctional triblock copolymer intended for targeted drug delivery applications has been designed and successfully synthesized. Following various controlled polymerization and modification steps, a saccharide end-functionalized polyoxyethylene block was attached through an aromatic imine bond, cleavable in slightly acidic conditions, to an amphiphilic diblock copolymer comprising a biodegradable hydrophobic block and a partially modified with mitochondria targeting ligands polycationic block. The micelles formed from the triblock copolymer in aqueous media possess key functions (cleavable "stealth" shield, targeting groups) needed for safe extracellular transport, successful cell internalization, and drug delivery to the target cellular organelles. The multifunctional nanocarriers were loaded with the plant-derived anticancer drug curcumin, and in vitro analyses revealed that their cytotoxic, apoptogenic, and NF-κB-inhibitory effects on target cells were superior over those of the free drug and non-functionalized polymer micelles of similar composition. Moreover, the enhanced cellular internalization and mitochondrial accumulation of the multifunctional nanocarriers compared to their non-functionalized analogues was visualized by fluorescence microscopy. The results indicate that the presented multifunctional micelles have a potential for application in nanomedicine for enhanced organelle-specific drug delivery.

Insulin/poly(ethylene glycol)-block-poly(L-lysine) Complexes: Physicochemical Properties and Protein Encapsulation.

Insulin (INS) was encapsulated into complexes with poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLys), which is a polypeptide-based block copolymer (a neutral-cationic block polyelectrolyte). The particular cationic-neutral block copolymer can complex INS molecules in aqueous media via electrostatic interactions. Light-scattering techniques are used to study the complexation process and structure of the hybrid nanoparticles in a series of buffers, as a function of protein concentration. The physicochemical and structural characteristics of the complexes depend on the ionic strength of the aqueous medium, while the concentration of PEG-b-PLys was constant through the series of solutions. As INS concentration increased the size distribution of the complexes decreased, especially at the highest ionic strength. The size/structure of complexes diluted in biological medium indicated that the copolymer imparts stealth properties and colloidal and biological stability to the complexes, features that could in turn affect the clearance properties in vivo. Therefore, these studies could be a rational roadmap for designing the optimum complexes/effective nanocarriers for proteins and peptides.

Chemical force microscopy of stimuli-responsive adhesive copolymers.

Atomic force microscopy with chemically sensitive tips was used to investigate the hydrophobic and electrostatic interaction forces of a stimuli-responsive adhesive polymer, and their dynamic changes in response to water immersion and salt concentration. Block copolymer-filled coatings were obtained by incorporating an amphiphilic block copolymer containing a polydimethylsiloxane (PDMS) block and a poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) block in a PDMS matrix. Topographic images of fresh samples revealed the presence of nanoscale domains associated with the presence of copolymers, covered by a thin layer of PDMS. Prolonged (30 days) immersion in aqueous solution led to the exposure of the hydrophilic PDMAEMA chains on the surface. Using adhesion force mapping with hydrophobic tips, we showed that fresh samples were uniformly hydrophobic, while aged samples exhibited lower surface hydrophobicity and featured nanoscale hydrophilic copolymer domains. Force mapping with negatively charged tips revealed remarkable salt-dependent force plateau signatures reflecting desorption of polyelectrolyte copolymer chains. These nanoscale experiments show how solvent-induced conformational changes of stimuli-responsive copolymers can be used to modulate surface adhesion.