Boronic Acid-containing Polymer Research Articles

Solute Stabilization Effects of Nanoparticles Containing Boronic Acids in the Absence of Binding Pairs.

Boronic acids are widely used in materials science because of their ability to reversibly bind with diol and catechol moieties through dynamic covalent interactions in a pH- and oxidative-dependent manner. Considerably fewer studies focus on property modulation of boronic acid-based materials in the absence of a biding pair. Herein, we discuss the effects of the boronic acid-containing polymer block length on solute release kinetics from nanoparticles in a stimuli-responsive manner for on-demand delivery. In this study, ABC-type linear amphiphiles of poly(d,l-lactide) and poly(2-methacryloyloxyethyl phosphorylcholine) containing a middle block functionalized with 3-aminophenylboronic acid were synthesized by a combination of ring-opening and controlled free radical polymerizations. Nile red-loaded nanoparticles were self-assembled using a multi-inlet vortex mixer in a well-controlled manner. Release was evaluated at pH above and below the pKa of the boronic acid and in the presence of hydrogen peroxide. Our results show that release kinetics from nanoparticles incorporating a boronic acid-functionalized interlayer were slower than those without it, and the rate could be modulated according to pH and oxidative conditions. These effects can be attributed to several factors, including the hydrophobicity of the boronic acid block as well as hydrogen bonding interactions existing between locally confined boronic acids. While boronic acids are generally utilized as boronic/boronate esters, their stabilizing effects in the absence of appropriate binding pairs are relevant and should be considered in the design of boronic acid-based technologies.

Multi-stimuli responsive boronic acid-containing polymers via recyclable nanoscale zerovalent iron (nZVI)-mediated photoRDRP in ionic liquid

A facile method based on recyclable nanoscale zero-valent iron (nZVI)-mediated photoRDRP in ionic liquid led to synthesis of narrow disperse poly(2-(dimethylamino)ethyl methacrylate) and poly(2-(dimethylamino)ethyl methacrylate)-block-poly(4-vinylphenylboronic acid) (PDMAEMA-b-PVPBA) diblock copolymers thereof. Stimuli response of the PDMAEMA-b-PVPBA copolymer against changes in pH, temperature and sugar concentration is assessed. Recyclability of the nZVI (catalyst) and ionic liquid (solvent) is established. Polymerization can be shut down or turned on simply by turning off or on the UV-A irradiation. This temporal control of the polymerization might be useful for wide use of the developed protocol for spatiotemporal “ON/OFF” control. DFT calculations are performed to get the geometry of the involved species.

Distinct color changes in hydrogen peroxide-responsive thin films consisting of boronic acid-containing polymers

A novel methodology for the preparation of hydrogen peroxide (H2O2)-responsive thin-film sensors that display distinct color changes was developed. Boronic acid-containing films were obtained through the copolymerization of boronic acid and tertiary amine monomers, acrylamide, and a crosslinker on a pattern-printed microscope slide. After immersing the thin films in an aqueous H2O2 solution, they were colored with anionic dye solutions containing fructose. The color of the thin films changed depending on the H2O2 concentration in the solutions. When the H2O2 concentration is low, the thin film adsorbs a cationic dye, whereas at higher H2O2 concentrations, it adsorbs an anionic dye. This indicates that the thin film was negatively charged before reacting with H2O2 and that the charge converted to positive following the reaction with H2O2. Changes in the parameters such as monomer composition, pH, and fructose concentration might affect the color change behavior. The H2O2-responsive thin films presented herein are advantageous for the development of H2O2 sensors because of their relatively simple preparation and non-complex organic synthesis. In addition, there is virtually no limitation to choosing dyes, and any kind of color change can be realized.

A Bio-synthetic Hybrid Hydrogel Formed under Physiological Conditions Consisting of Mucin and a Synthetic Polymer Carrying Boronic Acid.

Mucin-containing bio-synthetic hybrid hydrogel is successfully formed under physiological conditions upon mixing aqueous solutions of native mucin and synthetic polymers carrying boronic acids. The mechanical properties and stability of the hydrogel in physiological solutions, e.g., cell culture media, are tunable depending on the boronic acid content of polymers. The hydrogel dissolved in the physiological solutions releases native mucin and boronic acid-containing polymer, which can control the adhesion of mammalian cells to the surface.

Preparation of Self-Healable and Spinnable Hydrogel by Dynamic Boronate Ester Bond from Hyperbranched Polyglycerol and Boronic Acid-Containing Polymer

Intrinsic self-healing hydrogel materials have been studied by many researchers owing to their excellent durability and high applicability in the biomedical field. Herein, we report a self-healing hydrogel containing dynamic boronate ester bonds. First, low-molecular-weight hyperbranched polyglycerol (LMPG), containing cis-1,2- or 1,3-diols, was synthesized by cationic ring-opening polymerization of glycidol initiated from citric acid. Second, 4-vinylphenyl boronic acid and acrylamide were co-polymerized in the LMPG-containing alkaline solution used for preparing the hydrogel. The composition of vinyl monomers, LMPG, and chemical cross-linker affects the gel-formation and self-healing properties of the hydrogel. Interestingly, the prepared hydrogel with specific composition exhibits excellent extensibility, resulting in 416-fold (41,600%) elongation. The formation of a reversible boronate ester bond by a diol of LMPG and boronic acid of vinyl polymer enables flexible fiber spinning process by reducing the drawing stress. After fiber fabrication is completed, the reversible bonds act as permanent multi-cross-point under absence of water, thereby giving a high tensile strength (128 MPa) to the hydrogel-based fiber.

Natural Polyphenols Augment Cytosolic Protein Delivery by a Functional Polymer

Cytosolic protein delivery is of great importance for basic cell biology and the discovery of novel protein-based biotherapeutics. It remains a challenging task because of the limited binding sites on proteins and their relatively large size. As a result, most current approaches for cytosolic protein delivery need covalent modification on native proteins, which is usually involved with complicated synthesis, reduced protein bioactivity, and unexpected safety concerns. In this study, we proposed a novel strategy to deliver proteins of different molecular sizes and isoelectric points by specific recognitions between natural polyphenols and boronic acid-containing polymers. Protein molecules were decorated with polyphenols via noncovalent hydrogen-bond/hydrophobic interactions or reversible dynamic covalent bonds. The natural polyphenols increase the binding affinity between proteins and boronic acid-containing polymers, allow the release of bound proteins in acidic environments because of pH-sensitive property of catechol–boronate esters, and thus greatly promote the cytosolic delivery efficiency. This strategy showed robust efficiency in the delivery of various proteins such as bovine serum albumin, phycoerythrin, and ribonuclease A and maintained the protein bioactivity after intracellular release. The reported strategy permits the development of a polyphenol-involved polymer platform for cytosolic protein delivery.

Oriented Antibody Immobilization and Immunoassay Based on Boronic Acid-containing Polymer Brush

High sensitive immunoassay platforms have gained intense attention due to their vital roles in early-stage disease diagnosis and therapeutic information feedback. Although random covalent-binding of antibody has been widely adopted in immunoassays due to its simplicity and effectiveness, it readily loses its activity and fails to exhibit high antigen-binding capacity. In this work, copolymer of zwitterionic sulfobetaine methacrylate (SBMA) and glycidyl methacrylate (GMA) brushes were immobilized onto inert polypropylene (PP) via surface-initiated atom transfer radical polymerization (ATRP) based on biomimetic dopamine pretreatment. Subsequently, boronic acid (BA) groups were covalently bonded via active GMA units, followed by the introduction of oriented immobilization of antibody. Owing to the oriented immobilization of antibody facilitated by BA groups in polymer brush, the bioactivity of antibody is well preserved, which endows the surface with significantly enhanced antigen-binding capacity. Moreover, the existence of SBMA segments in polymer brushes renders the surface high resistance to nonspecific protein adsorption, significantly alleviating the signal interference of antigen recognition. This strategy could find potential applications in developing high sensitive immunoassay platforms based on the different substrates.

Electrospun boronic acid-containing polymer membranes as fluorescent sensors for bacteria detection

In this work, a boronic acid copolymer, poly(4-vinylphenylboronic acid-co-2-(dimethylamino)ethyl methacrylate-co-n-butyl methacrylate) (pVDB) was designed for the rapid detection of bacteria based on reversible boronate ester formation with the diol-rich saccharide moieties found on bacterial membranes. Electrospun nanofibre membranes were prepared from a blend of polyacrylonitrile (PAN) and pVDB, which was synthesized by free radical polymerization. The pVDB@PAN membranes were used as fluorescent bacterial biosensors, displaying a distinct emission at 538nm when in contact with bacteria cells. The fluorescence intensity showed a maximum intensity after 24h of contact with Staphyloccocus aureus or Escherichia coli, and this intensity increased proportionally with the pVDB content in the electrospun membranes. When in contact with Pseudomona putida, the membranes became non-responsive within 8h due to the rapid formation of a bacterial biofilm. This fouling phenomena blocked the membrane surface for fluorescence readings. The pVDB@PAN bionsensor allowed for the rapid detection of the early stages of bacterial colonization well before biofilm formation, which could be advantageous for the early identification of pathogenic bacteria and prevention of their spreading.

Synthesis and Applications of Boronic Acid-Containing Polymers: From Materials to Medicine.

Synthesis and Applications of Boronic Acid-Containing Polymers: From Materials to Medicine.

Multicolor saccharide-sensing chips created via layer-by-layer adsorption of boronic acid-containing polymers

A novel saccharide-sensing chip that shows a distinct color change was developed. The saccharide-responsive thin films were obtained on a pattern-printed microscope slide via a layer-by-layer method utilizing a boronic acid-containing polycation. After adsorption of anionic dyes, the thin films were immersed in aqueous saccharide solutions. As the saccharide concentration increased, the thin films showed a multi-patterned color change that enabled the quantification of saccharides using multi-colorimetric sensing.

A Multicolor Saccharide Sensing Chip Created by Layer-by-Layer Adsorption of a Boronic Acid-containing Polymer

A novel saccharide sensor array that shows distinct color change was developed. By the layer-by-layer method utilizing boronic acid-containing polycation and polyanion, saccharide-responsive thin films were obtained on a pattern-printed microscope slide. After adsorbing anionic dyes, the thin films were immersed in aqueous saccharide solutions. As saccharide concentration increased, the thin films clearly changed their color. Since the color changed occurred at different saccharide concentrations depending on anionic dyes, the sensor array showed a multipactor color change which enables us to quantify saccharides by a pattern-based sensing.

Multivalent interaction-based carbohydrate biosensors for signal amplification

Multivalent interaction between boronic acids immobilized on quartz crystal microbalance (QCM) sensor surface and the carbohydrates modified Au-nanoparticle (AuNP) has been demonstrated for the development of a sensitive carbohydrate biosensor. Briefly, a boronic acid-containing polymer (boropolymer) as multivalent carbohydrate receptor was oriented immobilized on the cysteamine coated electrode through isourea bond formation. Carbohydrates were conjugated to AuNPs to generate a multivalent carbohydrates moiety to amplify the response signal. Thus, the binding of the carbohydrate conjugated AuNPs to the boropolymer surface are multivalent which could simultaneously increase the binding affinity and specificity. We systematically studied the binding between five carbohydrates conjugated AuNPs and the boropolymer. Our studies show that the associate constant ( K a) was in the order of fucose < glucose < mannose < galactose < maltose. A linear response in the range from 23 μM to 3.83 mM was observed for mannose conjugated AuNPs and the boropolymer recognition elements, with the lower detection limit of 1.5 μM for the carbohydrate analytes. Furthermore, the multivalent binding between carbohydrates and boronic acids are reversible and allow the regeneration of boropolymer surface by using 1 M acetic acid so as to sequentially capture and release the carbohydrate analytes.

Synthesis and characterization of biotin chain-end functionalized boronic acid-containing polymer (boropolymer) as functional glyco-affinity macroligand

A biotin chain-end functionalized boronic acid-containing polymer (biotin boropolymer) as an oriented glyco-affinity macroligand for efficient carbohydrate and glycoconjugate purification and identification application was described. Briefly, the biotin boropolymer was synthesized via a biotin derivated arylamine initiated cyanoxyl-mediated free-radical polymerization in one-pot fashion. The specific streptavidin binding capacity of biotin boropolymer was confirmed by streptavidin–HABA assay, while the specific carbohydrate binding capacity of biotin boropolymer was evaluated by Alizarin Red S binding assay. Efficient glyco-capturing followed by direct MALDI mass spectrometry identification of the captured carbohydrate was demonstrated by using magnetic bead functionalized with the biotin boropolymer via streptavidin/biotin interaction.

Activation of lymphocyte proliferation by boronate-containing polymer immobilised on substrate: The effect of boron content on lymphocyte proliferation

This study demonstrates that boronic acid-containing polymers coated onto solid support function as synthetic mitogens for mouse lymphocytes. The polymer was synthesized by radical copolymerization of 3-acrylamidophenylboronic acid with dimethylacrylamide (poly(AAPBA-DMAA)). The boronic acid in the trigonal form in the copolymer activated lymphocytes, probably by crosslinkage to glycoprotein moieties on the plasma membrane surface, as in the case of lectin stimulation. A higher concentration of phenylboronic acid on the copolymer surface resulted in greater activation of lymphocytes, suggesting that the number of phenylboronic acid residues per unit area may be a crucial factor in lymphocyte proliferation. The proliferative response of lymphocytes was also affected by the surface wettability, probably due to a difference in the flexibility of polymer strands at the cell-polymer interface.