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Nature Communications Oct 2019Almost all commercial proteins are purified using ammonium sulfate precipitation. Protein-polymer conjugates are synthesized from pure starting materials, and the...
Almost all commercial proteins are purified using ammonium sulfate precipitation. Protein-polymer conjugates are synthesized from pure starting materials, and the struggle to separate conjugates from polymer, native protein, and from isomers has vexed scientists for decades. We have discovered that covalent polymer attachment has a transformational effect on protein solubility in salt solutions. Here, protein-polymer conjugates with a variety of polymers, grafting densities, and polymer lengths are generated using atom transfer radical polymerization. Charged polymers increase conjugate solubility in ammonium sulfate and completely prevent precipitation even at 100% saturation. Atomistic molecular dynamic simulations show the impact is driven by an anti-polyelectrolyte effect from zwitterionic polymers. Uncharged polymers exhibit polymer length-dependent decreased solubility. The differences in salting-out are then used to simply purify mixtures of conjugates and native proteins into single species. Increasing protein solubility in salt solutions through polymer conjugation could lead to many new applications of protein-polymer conjugates.
Topics: Electrophoresis, Polyacrylamide Gel; Polymerization; Polymers; Protein Conformation; Proteins; Salts; Solubility; Solutions
PubMed: 31624254
DOI: 10.1038/s41467-019-12612-9 -
Biomacromolecules Nov 2023Polymer nanoparticles have generated significant interest as delivery systems for therapeutic cargo. Self-immolative polymers (SIPs) are an interesting category of...
Polymer nanoparticles have generated significant interest as delivery systems for therapeutic cargo. Self-immolative polymers (SIPs) are an interesting category of materials for delivery applications, as the characteristic property of end-to-end depolymerization allows for the disintegration of the delivery system, facilitating a more effective release of the cargo and clearance from the body after use. In this work, nanoparticles based on a pH-responsive polymer poly(ethylene glycol)--(2-diisopropyl)amino ethyl methacrylate) and a self-immolative polymer poly[,-(diisopropylamino)ethyl glyoxylamide--,-(dibutylamino)ethyl glyoxylamide] (P(DPAEGAm--DBAEGAm)) were developed. Four particles were synthesized based on P(DPAEGAm--DBAEGAm) polymers with varied diisopropylamino to dibutylamino ratios of 4:1, 2:1, 2:3, and 0:1, termed 4:1, 2:1, 2:3, and 0:1 PGAm particles. The pH of particle disassembly was tuned from pH 7.0 to pH 5.0 by adjusting the ratio of diisopropylamino to dibutylamino substituents on the pendant tertiary amine. The P(DPAEGAm--DBAEGAm) polymers were observed to depolymerize (60-80%) below the particle disassembly pH after ∼2 h, compared to <10% at pH 7.4 and maintained reasonable stability at pH 7.4 (20-50% depolymerization) after 1 week. While all particles exhibited the ability to load a peptide cargo, only the 4:1 PGAm particles had higher endosomal escape efficiency (∼4%) compared to the 2:3 or 0:1 PGAm particles (<1%). The 4:1 PGAm particle is a promising candidate for further optimization as an intracellular drug delivery system with rapid and precisely controlled degradation.
Topics: Polymers; Drug Delivery Systems; Polyethylene Glycols; Nanoparticles; Hydrogen-Ion Concentration
PubMed: 37709729
DOI: 10.1021/acs.biomac.3c00630 -
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi =... Oct 2022Polymer micelles formed by self-assembly of amphiphilic polymers are widely used in drug delivery, gene delivery and biosensors, due to their special hydrophobic... (Review)
Review
Polymer micelles formed by self-assembly of amphiphilic polymers are widely used in drug delivery, gene delivery and biosensors, due to their special hydrophobic core/hydrophilic shell structure and nanoscale. However, the structural stability of polymer micelles can be affected strongly by environmental factors, such as temperature, pH, shear force in the blood and interaction with non-target cells, leading to degradations and drug leakage as drug carriers. Therefore, researches on the structural integrity and distribution of micelle-based carriers are very important for evaluating their therapeutic effect and clinical feasibility. At present, fluorescence resonance energy transfer (FRET) technology has been widely used in real-time monitoring of aggregation, dissociation and distribution of polymer micelles ( and vo). In this review, the polymer micelles, characteristics of FRET technology, structure and properties of the FRET-polymer micelles are briefly introduced. Then, methods and mechanism for combinations of several commonly used fluorescent probes into polymer micelles structures, and progresses on the stability and distribution studies of FRET-polymer micelles ( and ) as drug carriers are reviewed, and current challenges of FRET technology and future directions are discussed.
Topics: Micelles; Drug Carriers; Polymers; Fluorescence Resonance Energy Transfer; Polyethylene Glycols
PubMed: 36310492
DOI: 10.7507/1001-5515.202111040 -
Angewandte Chemie (International Ed. in... Jan 2020Mucoadhesive polymers are of significant interest to the pharmaceutical, medical device, and cosmetic industries. Polysaccharides possessing charged functional groups,...
Mucoadhesive polymers are of significant interest to the pharmaceutical, medical device, and cosmetic industries. Polysaccharides possessing charged functional groups, such as chitosan, are known for mucoadhesive properties but suffer from poor chemical definition and solubility, while the chemical synthesis of polysaccharides is challenging with few reported examples of synthetic carbohydrate polymers with engineered-in ionic functionality. We report the design, synthesis, and evaluation of a synthetic, cationic, enantiopure carbohydrate polymer inspired by the structure of chitosan. These water-soluble, cytocompatible polymers are prepared via an anionic ring-opening polymerization of a bicyclic β-lactam sugar monomer. The synthetic method provides control over the site of amine functionalization and the length of the polymer while providing narrow dispersities. These well-defined polymers are mucoadhesive as documented in single-molecule scale (AFM), bulk solution phase (FRAP), and ex vivo tissue experiments. Polymer length and functionality affects bioactivity as long, charged polymers display higher mucoadhesivity than long, neutral polymers or short, charged polymers.
Topics: Carbohydrates; Chitosan; Humans; Polymerization; Polymers
PubMed: 31701611
DOI: 10.1002/anie.201911720 -
Biomacromolecules Jan 2020Combining multiple stimuli-responsive functionalities into the polymer design is an attractive approach to improve nucleic acid delivery. However, more in-depth...
Combining multiple stimuli-responsive functionalities into the polymer design is an attractive approach to improve nucleic acid delivery. However, more in-depth fundamental understanding how the multiple functionalities in the polymer structures are influencing polyplex formation and stability is essential for the rational development of such delivery systems. Therefore, in this study the structure and dynamics of thermosensitive polyplexes were investigated by tracking the behavior of labeled plasmid DNA (pDNA) and polymer with time-resolved fluorescence spectroscopy using fluorescence resonance energy transfer (FRET). The successful synthesis of a heterofunctional poly(ethylene glycol) (PEG) macroinitiator containing both an atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain-transfer (RAFT) initiator is reported. The use of this novel PEG macroinitiator allows for the controlled polymerization of cationic and thermosensitive linear triblock copolymers and labeling of the chain-end with a fluorescent dye by maleimide-thiol chemistry. The polymers consisted of a thermosensitive poly(-isopropylacrylamide) (PNIPAM, N), hydrophilic PEG (P), and cationic poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA, D) block, further referred to as NPD. Polymer block D chain-ends were labeled with Cy3, while pDNA was labeled with FITC. The thermosensitive NPD polymers were used to prepare pDNA polyplexes, and the effect of the N/P charge ratio, temperature, and composition of the triblock copolymer on the polyplex properties were investigated, taking nonthermosensitive PD polymers as the control. FRET was observed both at 4 and 37 °C, indicating that the introduction of the thermosensitive PNIPAM block did not compromise the polyplex structure even above the polymer's cloud point. Furthermore, FRET results showed that the NPD- and PD-based polyplexes have a less dense core compared to polyplexes based on cationic homopolymers (such as PEI) as reported before. The polyplexes showed to have a dynamic character meaning that the polymer chains can exchange between the polyplex core and shell. Mobility of the polymers allow their uniform redistribution within the polyplex and this feature has been reported to be favorable in the context of pDNA release and subsequent improved transfection efficiency, compared to nondynamic formulations.
Topics: Acrylic Resins; Carbocyanines; DNA; Fluorescence Resonance Energy Transfer; Magnetic Resonance Spectroscopy; Methacrylates; Nylons; Plasmids; Polyethylene Glycols; Polymerization; Polymers; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Temperature
PubMed: 31500418
DOI: 10.1021/acs.biomac.9b00896 -
Biointerphases Dec 2018Dentin adhesive systems for composite tooth restorations are composed of hydrophilic/hydrophobic monomers, solvents, and photoinitiators. The adhesives undergo phase...
Dentin adhesive systems for composite tooth restorations are composed of hydrophilic/hydrophobic monomers, solvents, and photoinitiators. The adhesives undergo phase separation and concomitant compositional change during their application in the wet oral environment; phase separation compromises the quality of the hybrid layer in the adhesive/dentin interface. In this work, the adhesive composition in the hybrid layer can be represented using the phase boundaries of a ternary phase diagram for the hydrophobic monomer/hydrophilic monomer/water system. The polymer phases, previously unaccounted for, play an important role in determining the mechanical behavior of the bulk adhesive, and the chemomechanical properties of the phases are intimately related to the effects produced by differences in the hydrophobic-hydrophilic composition. As the composition of the polymer phases varies from hydrophobic-rich to hydrophilic-rich, the amount of the adsorbed water and the nature of polymer-water interaction vary nonlinearly and strongly correlate with the change in elastic moduli under wet conditions. The failure strain, loss modulus, and glass transition temperature vary nonmonotonically with composition and are explained based upon primary and secondary transitions observed in dynamic mechanical testing. Due to the variability in composition, the assignment of mechanical properties and the choice of suitable constitutive models for polymer phases in the hybrid layer are not straightforward. This work investigates the relationship between composition and chemomechanical properties of the polymer phases formed on the water-adhesive phase boundary using quasistatic and dynamic mechanical testing, mass transfer experiments, and vibrational spectroscopy.
Topics: Chemical Phenomena; Dental Cements; Mechanical Phenomena; Polymers; Quantitative Structure-Activity Relationship
PubMed: 30558430
DOI: 10.1116/1.5058072 -
International Journal of Molecular... Apr 2023The search for biocompatible and renewable materials for the next generation of energy devices has led to increasing interest in using biopolymers as a matrix component... (Review)
Review
The search for biocompatible and renewable materials for the next generation of energy devices has led to increasing interest in using biopolymers as a matrix component for the development of electric double-layer capacitors (EDLCs). However, using biopolymers as host matrices presents limitations in performance and scalability. At the same time, ionic liquids (ILs) have shown exceptional properties as non-aqueous electrolytes. This review intends to highlight the progress in integrating ILs and biopolymers for EDLC. While ILs have been used as solvents to process biopolymers and electrolyte materials, biopolymers have been utilized to provide novel chemistries of electrolyte materials via one of the following scenarios: (1) acting as host polymeric matrices for IL-support, (2) performing as polymeric fillers, and (3) serving as backbone polymer substrates for synthetic polymer grafting. Each of these scenarios is discussed in detail and supported with several examples. The use of biopolymers as electrode materials is another topic covered in this review, where biopolymers are used as a source of carbon or as a flexible support for conductive materials. This review also highlights current challenges in materials development, including improvements in robustness and conductivity, and proper dispersion and compatibility of biopolymeric and synthetic polymeric matrices for proper interface bonding.
Topics: Ionic Liquids; Biopolymers; Solvents; Polymers; Electrolytes
PubMed: 37175574
DOI: 10.3390/ijms24097866 -
Nature Communications Feb 2018Facile automated biomacromolecule synthesis is at the heart of blending synthetic and biologic worlds. Full access to abiotic/biotic synthetic diversity first occurred...
Facile automated biomacromolecule synthesis is at the heart of blending synthetic and biologic worlds. Full access to abiotic/biotic synthetic diversity first occurred when chemistry was developed to grow nucleic acids and peptides from reversibly immobilized precursors. Protein-polymer conjugates, however, have always been synthesized in solution in multi-step, multi-day processes that couple innovative chemistry with challenging purification. Here we report the generation of protein-polymer hybrids synthesized by protein-ATRP on reversible immobilization supports (PARIS). We utilized modified agarose beads to covalently and reversibly couple to proteins in amino-specific reactions. We then modified reversibly immobilized proteins with protein-reactive ATRP initiators and, after ATRP, we released and analyzed the protein polymers. The activity and stability of PARIS-synthesized and solution-synthesized conjugates demonstrated that PARIS was an effective, rapid, and simple method to generate protein-polymer conjugates. Automation of PARIS significantly reduced synthesis/purification timelines, thereby opening a path to changing how to generate protein-polymer conjugates.
Topics: Peptides; Polymerization; Polymers; Proteins; Solid-Phase Synthesis Techniques
PubMed: 29487296
DOI: 10.1038/s41467-018-03153-8 -
Environmental Pollution (Barking, Essex... Oct 2023The prevalence and adverse impacts of microplastics requires the identification of science-based abatement measures. Electrocoagulation treatment is a cost-effective...
The prevalence and adverse impacts of microplastics requires the identification of science-based abatement measures. Electrocoagulation treatment is a cost-effective oxidation process that removes numerous pollutants, including to some extent, microplastics. The performance of a custom-built electrocoagulation reactor was determined by calculating the removal efficiency. The effects of the oxidation process on polymer types (polyamide (PA), polyethylene (PE), polyethylene terephthalate (PET) and polypropylene (PP)) and shapes (fibres and fragments) were investigated in synthetic wastewater and laundry wastewater. The calculated removal efficiency suggested that electrocoagulation treatment was an effective technology for microplastics abatement. More fibres tended to be removed than fragments, viz. 92% fibres removed versus 88% fragments. The findings also demonstrated that specific polymers were preferentially removed, viz. PET > LDPE > PP > PA. Further analysis indicated that the electrocoagulation treatment affected microplastic polymers physically, viz. flaking and changed surface conditions, as well as chemically, viz. changes in vibrational energies of C-O-C stretching bonds, C=O stretching bonds, C-H stretching bonds and formation of reactive oxygen species (ROS). Our findings indicate that whilst seemingly effective, electrocoagulation treatment induces changes to microplastic polymers that could beneficially lead to degradation, and/or further fragmentation or breakdown and thereby potentially generating more bioavailable toxic nanoplastic byproducts.
Topics: Microplastics; Polymers; Plastics; Wastewater; Water Pollutants, Chemical; Polypropylenes; Nylons; Polyethylene; Polyethylene Terephthalates; Electrocoagulation; Environmental Monitoring
PubMed: 37442330
DOI: 10.1016/j.envpol.2023.122159 -
Journal of Controlled Release :... Dec 2015The development of drug delivery systems based on well-defined polymer nanostructures could lead to significant improvements in the treatment of cancer. The design of... (Review)
Review
The development of drug delivery systems based on well-defined polymer nanostructures could lead to significant improvements in the treatment of cancer. The design of these therapeutic nanosystems must account for numerous systemic and circulation obstacles as well as the specific pathophysiology of the tumor. Nanoparticle size and surface charge must also be carefully selected in order to maintain long circulation times, allow tumor penetration, and avoid clearance by the reticuloendothelial system (RES). Targeting ligands such as vitamins, peptides, and antibodies can improve the accumulation of nanoparticle-based therapies in tumor tissue but must be optimized to allow for intratumoral penetration. In this review, we will highlight factors influencing the design of nanoparticle therapies as well as the development of modern controlled "living" polymerization techniques (e.g. ATRP, RAFT, ROMP) that are leading to the creation of sophisticated new polymer architectures with discrete spatially-defined functional modules. These innovative materials (e.g. star polymers, polymer brushes, macrocyclic polymers, and hyperbranched polymers) combine many of the desirable properties of traditional nanoparticle therapies while substantially reducing or eliminating the need for complex formulations.
Topics: Animals; Antineoplastic Agents; Drug Delivery Systems; Humans; Nanostructures; Neoplasms; Polymerization; Polymers
PubMed: 26342661
DOI: 10.1016/j.jconrel.2015.08.054