Polyion Complex Research Articles

A high-throughput lysosome trafficking assay guides ligand selection and elucidates differences in CD22-targeted nanodelivery

ABSTRACT Targeted nanoparticles offer potential to selectively deliver therapeutics to cells; however, their subcellular fate following endocytosis must be understood to properly design mechanisms of drug release. Here we describe a nanoparticle platform and associated cell-based assay to observe lysosome trafficking of targeted nanoparticles in live cells. The nanoparticle platform utilizes two fluorescent dyes loaded onto PEG-poly(glutamic acid) and PEG-poly(Lysine) block co-polymers that also comprise azide reactive handles on PEG termini to attach antibody-based targeting ligands. Fluorophores were selected to be pH-sensitive (pHrodo Red) or pH-insensitive (Alexafluor 488) to report when nanoparticles enter low pH lysosomes. Dye-labelled block co-polymers were further assembled into polyion complex micelle nanoparticles and crosslinked through amide bond formation to form stable nano-scaffolds for ligand attachment. Cell binding and lysosome trafficking was determined in live cells by fluorescence imaging in 96-well plates and quantification of red- and green-fluorescence signals over time. The platform and assay was validated for selection of optimal antibody-derived targeting ligands directed towards CD22 for nanoparticle delivery. Kinetic analysis of uptake and lysosome trafficking indicated differences between ligand types and the ligand with the highest lysosome trafficking efficiency translated into effective DNA delivery with nanoparticles bearing the optimal ligand.

Polyion complex vesicles containing viscosity enhancer for sustained release of water-soluble low-molecular-weight drugs

Abstract Polyion complex vesicles (PICsomes) possess several features that render them as suitable for drug delivery systems. However, retaining water-soluble low-molecular-weight compounds (WLMWCs) remains challenging because of the high permeability of their vesicular membranes. Herein, we propose a new approach for prolonged retention and sustained release of WLMWCs from PICsomes by loading hydroxypropyl methylcellulose to increase the viscosity of the inner aqueous phase. The PICsomes retained 2% to 4% of the WLMWCs, and 100% of the WLMWCs were released within 96 h according to first-order kinetics.

Tuning of molecular weight and chemical composition of polyols obtained from Poly(ethylene terephthalate) waste recycling through the application of organocatalysts in an upcycling route

High molecular weight liquid polyols were produced from complex Poly (ethylene terephthalate) (PET) waste (low molecular weight PET waste, monolayer compounds, and coloured PET bottles) in one-step synthesis using mild reaction conditions. For the first time, a wide range of upcycled polyols were obtained by modulating the reaction conditions to control the chemical composition and molecular weight, in order to revalorize the same PET waste in different polyols.A new versatile, efficient, selective and sustainable chemical recycling method was developed, employing cheap reagents (ethylene carbonate) and basic organocatalysts, under mild reaction conditions (moderate temperatures and atmospheric pressure). Chemically, the polyols showed a singular composition, consisting of three types of repeating units, two coming from PET and one belonging to the ethylene carbonate ring-opening. Depending on the depolymerisation conditions of the PET waste and the catalyst used, the ratio between these moieties varied considerably, giving rise to a wide portfolio of liquid polyols. In addition, the ability of the organocatalyst to introduce the carbonate unit into the polyol chain was analysed as a function of the number of ethylene carbonate units used.As a proof of concept, these new liquid secondary raw materials served as a starting point for the synthesis of polyurethanes under standard conditions. Ultimately, the final objective of this upcycling process will be the application of a wide range of high-quality polyols as soft segments to produce more sustainable and high-performance polyurethanes (flexible foams, coatings, sealants, adhesives, elastomers).

Pathogen-responsive delivery of Nisin

Nisin, a food preservative commonly used in dairy and meat products, would be more effective if it was kept protected within a delivery system and its release accelerated in response to food contamination. Thus, nisin would remain stable in food for longer and only target harmful microorganisms. To achieve this goal, we describe here the first example of pathogen-responsive polyion complex (PIC) nanoparticles that release nisin preferentially in the presence of hyaluronidase-producing foodborne pathogens such as Staphylococcus aureus. In brief, we used a simple electrostatic complexation method with hyaluronic acid as an enzyme-degradable encapsulating polymer to produce small, well-defined spherical nisin-loaded PIC nanoparticles with good encapsulation efficiencies. These nisin-HA PIC nanoparticles displayed good stability at high salt concentrations, while the release of nisin was accelerated by hyaluronidase during in vitro experiments. More importantly, these nisin-HA PIC nanoparticles showed a better inhibitory effect against hyaluronidase-producing S. aureus than Bacillus cereus, a non-hyaluronidase-producing control. Finally, we performed a controlled contamination experiment to evaluate if these pathogen-responsive nanoparticles prevented microbial growth in milk, a representative food matrix. Remarkably, these nisin-HA PIC nanoparticles showed the same inhibitory effect as free nisin against hyaluronidase-producing S. aureus while having a minimal impact on non-hyaluronidase-producing B. cereus. Altogether, our findings highlight the potential of pathogen-triggered nisin release, suggesting innovative avenues for optimizing the delivery of this food preservative.

Multi-stimuli-responsive shape memory flexible composites based on magnetic melamine/polydopamine/phosphorene complex foams and polyethylene glycol

We have developed a novel type of flexible multi-stimuli-responsive shape memory composite system based on a melamine/polydopamine (PDA)/Fe3O4/phosphorene (PR) complex foam and poly(ethylene glycol) (PEG). The system was constructed through coating PDA on the skeleton of the melamine foam and then decorating the PDA layer with Fe3O4 and PR nanosheets, followed by vacuum impregnation of PEG. The resultant composites exhibit an intrinsic thermal-driven shape memory behavior with a high shape recovery ratio of around 100% thanks to their high latent heat capacity derived from the loaded PEG. The introduction of magnetic Fe3O4 nanoparticles and PR nanosheets not only enhances the thermal conductance of the composites but also generates good magnetic and photothermal responsiveness. This enables the composites to obtain good light- and magnetic-driven shape memory capabilities in a shorter shape recovery period. This study offers a new strategy for developing smart materials with multiple and effective response to light, heat, and magnetism.

Interfacing as embodied practice: journeys between print, screen and beyond

ABSTRACT This paper develops a concept of interfacing as a heterogeneous zone of interaction, a relational space created by users as they bring together interact with and draw on a range of digital and analogue materials, sources and technologies. It examines the ways tourists and travellers access, engage, use, transfer and blend multiple media sources drawing across both analogue and digital sources as they plan, execute and reflect on the trips and visits they make. It derives from a series of in depth ‘show and tell’ style interviews with 18 participants recruited in the UK. It contributes to the growing literature on digital geographies by exploring the relational spatiality by which individuals build interfacing activities around specific tasks and experiences as heterogeneous and contingent socio-material spaces. It develops a conception of interfacing around two interrelated and iterative sets of embodied practices. These are firstly, assembling and mobilising and secondly intermediating and sense making. Using this twin conception of interfacing as an active making, the paper discusses how and where a conception of interfacing as embodied practice might contribute to understandings of human digital relationships within complex poly media situations and environments.

Crystal structure of poly[hexa-μ-bromido-bis{2-[1-(pyridin-2-yl)ethylideneamino]ethanolato}tetracopper(II)

The reaction of the Schiff base 2-[1-(pyridin-2-yl)ethylideneamino]ethanol (HL), which is formed by reaction of 2-aminoethanol and 2-acetylpyridine with CuBr2 in ethanol results in the isolation of the new polymeric complex poly[hexa-μ-bromido-bis{2-[1-(pyridin-2-yl)ethylideneamino]ethanolato}tetracopper(II)], [Cu4Br6(C9H11N2O)2] n or [Cu4Br6 L 2] n . The asymmetric unit of the crystal structure of the polymeric [Cu4Br6 L 2] n complex is composed by four copper (II) cations, two monodeprotonated molecules of the ligand, and six bromide anions, which act as bridges. The ligand molecules act in a tridentate fashion through their azomethine nitrogen atoms, their pyridine nitrogen atoms, and their alcoholate O atoms. The crystal structure shows two types of geometries in the coordination polyhedrons around Cu2+ ions. Two copper cations are situated in a square-based pyramidal environment, while the two other copper cations adopt a tetrahedral geometry. Bromides anions acting as bridges between two metal ions connect the units, resulting in a tetranuclear polymer compound.

Synthesis of an Alternating Polycation with the Dense 1,2,3-Triazole Backbone

AbstractPolycations are an important class of water-soluble polymers because they form polyion complexes with DNA. Thus, the synthesis of polycations with controlled monomer sequences will be of increasing importance for the formation of well-defined polyion complexes. In this study, cationic homopolymer and alternating copolymer with the dense triazole backbone were synthesized by copper(I)-catalyzed azide–alkyne cycloaddition polymerization. The polycations obtained were characterized by potentiometric and turbidimetric titrations, and by complex formation with poly(acrylic acid).

PH-Induced Mechanical Transition in Polyion Complex Hydrogels: Shifting from Ionic Association to Hydrophobic Association

pH-Induced Mechanical Transition in Polyion Complex Hydrogels: Shifting from Ionic Association to Hydrophobic Association

Trapping waste metal ions in a hydrogel/coal powder composite for boosting sewage purification via solar-driven interfacial water evaporation with long-term durability

The improper disposal of effluents contaminated with waste metal ions poses significant threats to clean water resources. Recently, solar-driven interfacial water evaporation has gained increasing interests for sustainable water purification, nevertheless, the presence of various hydrated metal ions from industrial effluents makes it challenging for conventional distillers to achieve efficient purification performances. Herein, a waste metal ion trapping strategy based on a novel solar vapor generator (SVG) toward highly efficient solar-driven sewage purification with prolonged durability is reported. This SVG is constructed based on a polyion complex (PIC) hydrogel/coal powder composite (PCC), where the PIC skeleton provides metal ion entrapment capabilities, and the low-cost coal powders act as solar absorbents. PCC enables improved solar-driven sewage purification from two aspects: first, the entrapped multivalent ions help to activate the water molecules inside PCC and lower water evaporation enthalpy, leading to enlarged evaporation rate; second, the strong interactions between the multivalent metal ions and polyelectrolyte chains aid in stabilizing their porous structure and maintaining continuous water transport capabilities. The resultant PCC-based SVG demonstrated high evaporation rate up to 3.6 kg · m−2· h−1 in simulated industrial sewage under one sun illumination, as well as stable and efficient clean water generation in actual coal washery wastewater even for three weeks. We envision that the rational design of SVG with ions trapping capabilities and cost-effective solar absorbers should broaden the practical applications of SVG for harsh wastewater treatment.

Improving the Sustainability of Catalytic Glycolysis of Complex PET Waste through Bio-Solvolysis.

This work addresses a novel bio-solvolysis process for the treatment of complex poly(ethylene terephthalate) (PET) waste using a biobased monoethylene glycol (BioMEG) as a depolymerization agent in order to achieve a more sustainable chemical recycling process. Five difficult-to-recycle PET waste streams, including multilayer trays, coloured bottles and postconsumer textiles, were selected for the study. After characterization and conditioning of the samples, an evaluation of the proposed bio-solvolysis process was carried out by monitoring the reaction over time to determine the degree of PET conversion (91.3-97.1%) and bis(2-hydroxyethyl) terephthalate (BHET) monomer yield (71.5-76.3%). A monomer purification process, using activated carbon (AC), was also developed to remove the colour and to reduce the metal content of the solid. By applying this purification strategy, the whiteness (L*) of the BHET greatly increased from around 60 to over 95 (L* = 100 for pure white) and the Zn content was significantly reduced from around 200 to 2 mg/kg. The chemical structure of the purified monomers was analyzed via infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC), and the composition of the samples was measured by proton nuclear magnetic resonance (1H-NMR), proving a high purity of the monomers with a BHET content up to 99.5% in mol.

Diffusive delivery of plasmid DNA using zwitterionic carboxyalkyl poly(1-vinylimidazole) into skeletal muscle in vivo.

Zwitterionic carboxyalkyl poly(1-vinylimidazole) (CA-PVIm) polymers with imidazolium cations and carboxylate anions have been synthesized as a carrier for the in vivo delivery of plasmid DNA (pDNA) to skeletal muscle. From differential scanning calorimetry measurements, resulting CA-PVIm had intermediate water in hydration water as a biocompatible polymer. Notably, when the pDNA and resulting CA-PVIm were mixed, slight retarded bands of the pDNA were observed in agarose gel electrophoresis, suggesting the polyion complex (PIC) formation between the pDNA and CA-PVIm despite zwitterionic polymers. Resulting PICs maintained the higher-order structure of the pDNA. Using resulting pDNA PICs, the highest pDNA expression by intramuscular injection was achieved in the PIC with 7 mol% carboxymethylated PVIm, that is, CA1(7)-PVIm, observed in a widespread area by in vivo imaging system. These results suggest that the CA1(7)-PVIm/pDNA PIC is effective for the diffusive delivery of the pDNA into skeletal muscle for the treatment of serious muscle diseases.

Stable and permeable polyion complex vesicles designed as enzymatic nanoreactors.

Polymeric vesicles are perspective vehicles for fabricating enzymatic nanoreactors towards diverse biomedical and catalytic applications, yet the design of stable and permeable vesicles remains challenging. Herein, we developed polyion complex (PIC) vesicles featuring high stability and a permeable membrane for adequate enzyme loading and activation. Our design relies on co-assembly of an anionic diblock copolymer (PSS96-b-PEO113) with cationic branched poly(ethylenimine) (PEI). The polymer combination endows strong electrostatic interaction between the PSS and PEI building blocks, so their assembly can be implemented at a high salt concentration (500 mM NaCl), under which the charge interaction of the enzyme-polymer is inhibited. This control realizes the successful and safe loading of enzymes associated with the formation of stable PIC vesicles with an intrinsic permeable membrane that is favourable for enhancing enzymatic activity. The control factors for vesicle formation and enzyme loading were investigated, and the general application of loading different enzymes for cascade reaction was validated as well. Our study reveals that proper design and combination of polyelectrolytes is a facile strategy for fabricating stable and permeable polymeric PIC vesicles, which exhibit clear advantages for loading and activating enzymes, consequently boosting their diverse applications as enzymatic nanoreactors.

Triphenylphosphonium-modified catiomers enhance in vivo mRNA delivery through stabilized polyion complexation.

Nanocarriers based on cationic materials play a central role in the success of mRNA-based therapies. Traditionally, amine-bearing lipids and polymers have been successfully employed for creating mRNA-loaded nanocarriers, though they still present challenges, such as physical and biological instability, limiting both delivery efficiency and therapeutic potential. Non-amine cations could be a promising avenue in addressing these limitations. However, such alternatives remain notably underexplored. Herein, we introduced triphenylphosphonium (TPP) as an alternative cationic moiety for mRNA delivery, leveraging its advantageous properties for nucleic acid complexation. Through the modification of amine-bearing catiomers, we replaced traditional amine-based counterparts with TPP to create innovative polymeric micelles as mRNA nanocarriers. A comprehensive analysis, encompassing physicochemical, thermodynamic, and computational approaches, revealed that the TPP substitution significantly influenced polymer self-assembly, mRNA binding, and the overall stability of mRNA-loaded polymeric micelles. Upon intravenous injection, TPP-bearing micelles demonstrated a remarkable increase in mRNA bioavailability, facilitating efficient protein production in solid tumors. These findings provide a compelling rationale for substituting amines with TPP, emphasizing their potential for advancing mRNA therapeutics.

Effective design of PEGylated polyion complex (PIC) nanoparticles for enhancing PIC internalisation in cells utilising block copolymer combinations with mismatched ionic chain lengths.

In nanomedicine, PEGylation of nanomaterials poses a dilemma since it inhibits their interaction with target cells and enables their retention in target tissues despite its biocompatibility and nonspecific internalisation suppression. PEGylated polypeptide-based polyion complexes (PICs) are fabricated via the self-assembly of PEGylated aniomers and homocatiomers based on electrostatic interactions. We propose that various parameters like block copolymer design and PIC domain characteristics can enhance the cell-PEGylated PIC interactions. Remarkably, the properties of the PIC domain were tuned by the matched/mismatched ionomer chain lengths, PIC domain crosslinking degree, chemical modification of cationic species after crosslinking, PIC morphologies (vesicles/micelles) and polyethylene glycol (PEG) chain lengths. Cellular internalisation of the prepared PICs was evaluated using HeLa cells. Consequently, mismatched ionomer chain lengths and vesicle morphology enhanced cell-PIC interactions, and the states of ion pairing, particularly cationic residues, affected the internalisation behaviours of PICs via acetylation or guanidinylation of amino groups on catiomers. This treatment attenuated the cell-PIC interactions, possibly because of reduced interaction of PICs with negatively charged species on the cell-surface, glycosaminoglycans. Moreover, morphology and PEG length were correlated with PIC internalisation, in which PICs with longer and denser PEG were internalised less effectively. Cell line dependency was tested using RAW 264.7 macrophage cells; PIC recognition could be maintained after capping amino groups on catiomers, indicating that the remaining anionic groups were still effectively recognised by the scavenger receptors of macrophages. Our strategy for tuning the physicochemical properties of the PEGylated PIC nanocarriers is promising for overcoming the PEG issue.

Hybrid polyionic complexes as nanoreactors for the synthesis of iron oxide nanoparticles: From size control to modulation of magnetic and catalytic properties

Hybrid polyion complexes (HPICs) obtained from the complexation in aqueous solution of a double hydrophilic block copolymers and metal ions can act as efficient precursors for the controlled synthesis of hybrid nanoparticles. Hence, HPICs based on a mixture of ferrous and ferric ions with poly(ethylene oxide)-block-poly(acrylic acid) were used to initiate, after the addition at 70 °C of a solution of NH4OH, the formation of iron oxide nanoparticles. The careful choice of the molar ratio between polymer and metal ions within HPICs enables to tune the morphology and size of the obtained iron oxide nanoparticles while maintaining the same surface composition. This control of size and composition was further used to highlight the relationship between the size of these particles and their catalytic and magnetic properties.

Knockdown of BACE1 by a multistage brain-targeting polyion complex improved memory and learning behaviors in APP/PS1 transgenic mouse model

Cleavage of Amyloid precursor protein (APP) by the β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting step in the production of amyloid-β (Aβ) synaptotoxins. The siRNA-mediated silencing to attenuate the expression of BACE1 to ameliorate cognitive dysfunction in mice had been investigated. To improve therapeutic gene delivery to the central nervous system, cationic copolymer poly(ethylene glycol)-b-poly[N-(N′-{N′′-[N′′′-(2-aminoethyl)-2-aminoethyl]-2-aminoethyl}-2-aminoethyl)aspartamide]-cholesterol was synthesized, then RVG29 and Tet1 peptides were exploited as ligands to construct a dual-targeting brain gene delivery polyion complex (Tet1/RVG29-PIC). The cell uptake of a coculture cell model showed that the Tet1/RVG29-PIC exhibited notable transport characteristics and possessed affinity towards nerve cells. In vivo transfection, Tet1/RVG29-PIC possessed the highest expression of luciferase in brain compared with that of RVG29-PIC or Tet1-PIC, which were 1.25 and 1.22 times respectively. Silence BACE1 expression using siRNA-expressing plasmid loaded Tet1/RVG29-PIC that improved behavioral deficits in the APP/PS1 mouse model, demonstrating the favorable brain delivery properties of Tet1/RVG29-PIC by synergistical engagement of GT1B and nicotinic acetylcholine receptors. Our results suggested that the nanoformulation has the potential to be exploited as a multistage-targeting gene vector for the CNS disease therapy.

A REVIEW ON IMPROVISED EXPLOSIVE DEVICES AND THE HUMANITARIAN HARM CAUSED BY THEM

Improvised explosive devices (IEDs) in all their forms have emerged as the most serious threat. These devices can range from simple explosive devices to complex military systems using high-grade explosives. A thorough grasp of the many types of devices and their effects is required for proper mass casualty event planning and management of the complex poly trauma victims that they usually bring. They may wreak havoc on a landscape. Depending on the desired target, they can be initiated in a variety of ways. As a result, there is a pressing need to research and ameliorate the mechanism of extremities harm induced by these devices. These improvised explosive devices are generally uncommonly encountered outside the battlefield. The majorities of vulnerability evaluations presume that an improvised explosive device would attain maximal TNT equivalency and detonate effectively. They are still a popular terrorist weapon. These are unusual explosive weapons that can be used in a variety of ways to cause injury, fatalities, and destruction of property in both military and civilian conditions. IEDs continue to be a domestic menace. The science and damage profile of these devices are described in this review. The humanitarian devastation inflicted by IEDs is thus depicted. KEYWORDS: - improvised explosive devices, explosives, detonation, injury, impact testing, biomechanics, ground penetrating radar, detection, prevention, National Bomb Data Centre

A micro-fragmented collagen gel as a cell-assembling platform for critical limb ischemia repair

Critical limb ischemia (CLI) is a devastating disease characterized by the progressive blockage of blood vessels. Although the paracrine effect of growth factors in stem cell therapy made it a promising angiogenic therapy for CLI, poor cell survival in the harsh ischemic microenvironment limited its efficacy. Thus, an imperative need exists for a stem-cell delivery method that enhances cell survival. Here, a collagen microgel (CMG) cell-delivery scaffold (40 × 20 μm) was fabricated via micro-fragmentation from collagen–hyaluronic acid polyionic complex to improve transplantation efficiency. Culturing human adipose-derived stem cells (hASCs) with CMG enabled integrin receptors to interact with CMG to form injectable 3-dimensional constructs (CMG-hASCs) with a microporous microarchitecture and enhanced mass transfer. CMG-hASCs exhibited higher cell survival (p < 0.0001) and angiogenic potential in tube formation and aortic ring angiogenesis assays than cell aggregates. Injection of CMG-hASCs intramuscularly into CLI mice increased blood perfusion and limb salvage ratios by 40 % and 60 %, respectively, compared to cell aggregate-treated mice. Further immunofluorescent analysis revealed that transplanted CMG-hASCs have greater muscle regenerative and angiogenic potential, with enhanced cell survival than cell aggregates (p < 0.05). Collectively, we propose CMG as a cell-assembling platform and CMG-hASCs as promising therapeutics to treat CLI.

Site-Specific Polymerization-Induced Electrostatic Self-Assembly: Synthesis of Highly Charged Salt-Tolerant Polyion Complex Nanoreactors

Site-Specific Polymerization-Induced Electrostatic Self-Assembly: Synthesis of Highly Charged Salt-Tolerant Polyion Complex Nanoreactors