Block Glycopolymers Research Articles

Lung-targeted thermosensitive double-hydrophilic block glycopolymer micelles by RAFT polymerization

Lung-targeted thermosensitive double-hydrophilic block glycopolymer micelles by RAFT polymerization

Synthesis and Self-Assembly of Well-Defined pH-Responsive Block Glycopolymers

Two pH-responsive block glycopolymers, poly (ethylene glycol)-b-Poly (2- (diethylamino) ethyl methacrylate-co-2-gluconamidoethyl methacrylate) (PEG113-b-P(DEA55-co-GAMA12)) and poly (ethylene glycol)-b-poly (2-(diethylamino) ethyl methacrylate)-b-poly (2-gluconamido ethyl methacrylate) (PEG113-b-PDEA55-b-PGAMA15), were synthesized via atom transfer radical polymerization (ATRP) by directly or successively polymerization of GAMA and DEA monomers using a PEG-based macroinitiator, respectively, without protecting group chemistry. Those block glycopolymers were confirmed by proton Nuclear Magnetic Resonance (1H NMR) and Gel Permeation Chromatography (GPC), and their self-assembly behaviors were characterized by Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS) and Zeta-potential. The results show both synthetic block glycopolymers were dissolved molecularly in aqueous solution at acidic pH (such as pH 3), thus it can reversibly convert to be two-layer micelles comprising DEA and GAMA cores, PEG coronas with size of around 50 nm, or micelles comprising DEA cores, GAMA and PEG outer coronas with bigger size of 70 nm for PEG113-b- P(DEA55-co-GAMA12) and PEG113-b-PDEA55-b-PGAMA15), respectively, at basic condition. Both glycopolymers have the micellization process at middle pH (pH 6-8), but possess different isoelectric points (pIs) (at pH 8.0 and 7.8) for their pH responsive block of PEG113-b-P(DEA55-co-GAMA12) and PEG113-b-PDEA55-b-PGAMA15 with DEA-co-GAMA random structure or DEA chain only, respectively. This study not only reveals the self-assembly of pH responsive block glycopolymers with different architectures by fixing similar degree polymerization (DP) of their blocks, but also provides a tool to investigate pH induced dynamic covalent interaction between glycopolymers and phenylboronic acid derivatives or a light for designing novel drug delivery carriers.

Aqueous RAFT synthesis of block and statistical copolymers of 2-(α-d-mannopyranosyloxy)ethyl methacrylate with 2-(N,N-dimethylamino)ethyl methacrylate and their application for nonviral gene delivery

Statistical and block glycopolymers presenting d-mannose were prepared by aqueous RAFT polymerization, and the effect of the microstructure on gene delivery was examined.

Gold Nanorods Functionalized with Self-assembled Glycopolymers for Ultrasensitive Detection of Proteins

Abstract New, stable, and glyoco-derivatized gold nanorods (GNRs) were prepared using developed amphiphilic block glycopolymers poly[(lactose)m-b-(pyridine)n] to engineer self-organized, densely packed glycopolymeric recognition layers and generate a multivalent binding cavity onto the gold surface. We report a rapid and ultrasensitive biosensing for the weak affinity of protein–carbohydrate binding employing a combination of the longitudinal SPR of GNRs and the cluster glycoside effect. Thus, a very small amount of lectin (100 pg mL−1 = 8.3 × 10−13 M) was detected by the aggregation of GNRs.

From Polymer Sequence Control to Protein Recognition: Synthesis, Self-Assembly and Lectin Binding

A novel, highly efficient methodology to synthesize gradient glycopolymers has been successfully developed involving concurrent enzymatic monomer transformation and reversible addition–fragmentation chain transfer (RAFT) polymerization. By synchronizing enzymatic monomer transformation with polymerization, a continuous supply of the second monomer (glycomonomer) is achieved during the polymerization, resulting in a gradient sugar distribution in the final polymer. Detailed studies of the process using GPC and NMR indicate that the gradient glycopolymers synthesized by RAFT were well controlled. Subsequently, 1,2:3,4-di-O-isopropylidene-6-O-methacryloyl-α-d-galactopyranose (DIMAG) moieties were deprotected to regenerate the sugar and achieve amphiphilic bioactive glycopolymers. We demonstrate the synthesis of a set of glycopolymers with different sequential structures, such as statistical, gradient and block glycopolymers. The glycopolymers with block structure show higher affinities toward the RCA120 lect...

A biocompatible block glycopolymeric dispersant: synthesis, characterization, and dispersing properties for nano-TiO2

A biocompatible block glycopolymer poly(methyl methacrylate)-b-poly(3-O-allyl-α-D-glucose) (PMAG) was employed as a polymeric dispersant for the dispersion of nano-TiO2. PMAG was prepared from methyl methacrylate (MMA) and 3-O-allyl-1,2:5,6-di-O-isopropynylene-α-D-glucose (ADG) via reversible addition-fragmentation chain transfer (RAFT) polymerization. The obtained product was characterized by Fourier transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, and gel permeation chromatography (GPC). The copolymer showed good biocompatiblity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The maximum adsorption capacity for PMAG on nano-TiO2 is 4.11 mg/g, which is in good agreement with Langmuir isotherm. Transmission electron microscopy (TEM) image indicated that nano-TiO2 is well dispersed by PMAG. Raman and FT-IR spectra demonstrated that PMAG is absorbed onto the surface of nano-TiO2.

Dendritic Cell Lectin-Targeting Sentinel-like Unimolecular Glycoconjugates To Release an Anti-HIV Drug

A series of cyclodextrin-based glycoconjugates, including glycoclusters and star glycopolymers, were synthesized via combination of CuAAC Huisgen coupling and copper-mediated living radical polymerization. These glycoconjugates showed high affinity binding to the human transmembrane lectin DC-SIGN and act as inhibitors to prevent the binding of HIV envelope protein gp120 to DC-SIGN at nanomolar concentrations. The star block glycopolymers showed high loading capacity of hydrophobic anticancer and anti-HIV drugs, indicating promising applications in HIV-therapeutic and smart drug delivery.

Lectin recognizing thermoresponsive double hydrophilic glycopolymer micelles by RAFT polymerization

Thermoresponsive double hydrophilic block glycopolymer micelles can recognize lectin on the different temperature.

Phenylboronate-diol crosslinked glycopolymeric nanocarriers for insulin delivery at physiological pH.

Research into polymers with glucose-sensitivity in physiological conditions has expanded recently due to their therapeutic potential in diabetes. Herein, to explore the glucose-responsive properties of a new polymer under physiological conditions, we synthesized an amphiphilic block glycopolymer based on phenylboronic acid and a carbohydrate, which was named poly(d-gluconamidoethyl methacrylate-block-3-acrylamidophenylboronic acid) (p(AAPBA-b-GAMA)). Based on the cross-linking between the diol groups of the carbohydrates and phenylboronic acid, the glycopolymers self-assembled to form nanoparticles (NPs). The glucose-sensitivity was revealed by the swelling behavior of the NPs at different glucose concentrations and was found to be dependent on the glucose level. The morphology of the NPs revealed by transmission electron microscopy showed that the NPs were spherical in shape with good dispersity. The cell viability of the NPs investigated by MTT assay was more than 90%, indicating that the glycopolymers had good cytocompatibility. Insulin could be loaded onto the glycopolymer NPs with high efficiency (up to 10%), and insulin release increased with enhancement of the glucose level in the medium. Such a glucose-responsive glycopolymer is an excellent candidate that holds great potential in the treatment of diabetes.

Controlled block glycopolymers able to bind specific proteins

AbstractThe syntheses of a variety of amphiphilic block glycopolymers based on 2‐{[(D‐glucosamin‐2‐N‐yl)carbonyl]oxy}ethyl acrylate and n‐butyl acrylate or methyl methacrylate by single‐electron transfer‐living radical polymerization (SET‐LRP) are described. In a first step, the homopolymerization of unprotected acrylic glycomonomer to obtain well‐controlled glycopolymers is studied. Posterior and based on these studies, di‐ and triblock glycopolymers were synthesized via SET‐LRP of the glycomonomer from different hydrophobic blocks, varying the hydrophilic block lengths. All the copolymers are characterized by nuclear magnetic resonance spectroscopy and GPC. Moreover, their water solution behavior by dynamic light scattering and their capacity of interaction with Concanavalin A lectin by turbidimetry are analyzed. The effect on the block glycopolymers behavior of hydrophobic block nature and the length of glycopolymer segments is evaluated. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013

Tethering of Homo and Block Glycopolymer Chains onto Montmorillonite Surface by Atom Transfer Radical Polymerization

Well-defined homo glycopolymer/montmorillonite (MMT) nanocomposite (gly1) was prepared successfully by the “grafting from” technique from the modified surface of MMT via surface initiated atom transfer radical polymerization (SI-ATRP) of 3-O-methacryloyl-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (gly) in the presence of Cu(I)Br/ bi- pyridyl at 90?C in xylene. Well-defined diblock copolymers (gly2, gly3, gly4 and gly5) were also synthesized via the same technique by using comonomers of methylmethacrylate (MMA) or styrene (St) with glycomonomer (gly) using the same catalytic system. The formed nanocomposites showed both intercalated and exfoliated structures, as judged by XRD and TEM measurements. Further analyses were performed on such nanocomposites to confirm their formation such as TGA and DSC. The structures of the attached polymers to MMT were characterized by 1H NMR.

Breath figures method to control the topography and the functionality of polymeric surfaces in porous films and microspheres

AbstractPolymeric films with porous structures and microsphere patterns were prepared by the method of breath figures, mixing poly(methyl methacrylate) (PMMA) and amphiphilic copolymers containing glucose moieties in their structure, glycopolymers. Statistical and block glycopolymers were used in a proportion of 10 wt %. The statistical glycopolymers were synthesized via conventional free radical copolymerization, whereas the block copolymer of methyl methacrylate and 2‐{[(D‐glucosamin‐2‐Nyl) carbonyl]oxy}ethyl methacrylate, PMMA‐b‐PHEMAGl, was obtained by atom transfer radical polymerization. Glycopolymers were blended with a high molecular weight PMMA matrix and dissolved in a mixture of tetrahydrofuran and a small amount of water. Results showed that, depending on experimental conditions (water content, humidity, and type of copolymer), the observed final film morphology changes significantly. Thus, films with honeycomb pattern structures, spherical particles, or a mixture of both were obtained. In addition, polar glucose moieties were oriented principally either inside of the pores in the case of films and towards the surface in the case of particles. The specific surface bioactivity of these materials was examined using the specific lectin concanavalin A conjugated with fluorescein, Con A‐FITC. The successful binding of the Con A was demonstrated by fluorescence microscopy being more intense at the surface of the pores and of the particles. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Synthesis of glucose-sensitive block glycopolymers based on phenylboronic acid via raft polymerization

Synthesis of glucose-sensitive block glycopolymers based on phenylboronic acid via raft polymerization

Amphiphilic block glycopolymers via atom transfer radical polymerization: Synthesis, self-assembly and biomolecular recognition

In this work the synthesis of poly(butyl acrylate)-b-poly(2-{[(D-glucosamin-2-N-yl)carbonyl]oxy}ethyl methacrylate) (PBA-b-PHEMAGl) diblock glycopolymer and poly(2-{[(D-glucosamin-2-N-yl)carbonyl]oxy}ethyl methacrylate)-b-poly(butyl acrylate)-b-poly(2-{[(D-glucosamin-2-N-yl)carbonyl]oxy}ethyl methacrylate) (PHEMAGl-b-PBA-b-PHEMAGl) was performed via atom transfer radical polymerization. Monofunctional and difunctional poly(butyl acrylate) macroinitiators were used to synthesize the well-defined diblock and triblock glycopolymers by chain extension reaction with the glycomonomer HEMAGl. The self-assembly of these glycopolymers in aqueous solution was studied by dynamic light scattering and transmission electron microcopy, showing the coexistence of spherical micelles and polymeric vesicles. In addition, the biomolecular recognition capacity of these micelles and vesicles, containing glucose moieties in their coronas, was investigated using the lectin Concanavalin A, Canavalia Ensiformis, which specifically interacts with glucose groups. The binding capacity of Concanavalin A with glycopolymer is influenced by the copolymer composition, increasing with the length of HEMAGl glycopolymer segment in the block copolymer. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

Glycoparticles and bioactive films prepared by emulsion polymerization using a well-defined block glycopolymer stabilizer

A well-defined amphiphilic diblock glycopolymer of poly(2-{[(D-glucosamin-2-N-yl)carbonyl]oxy}ethyl methacrylate)-b-poly(butyl methacrylate) (PHEMAGl-b-PBMA) was synthesized via atom transfer radical polymerization (ATRP). Due to its capability to form micelles in aqueous solution, the obtained block glycopolymer was used as polymeric surfactant in the emulsion polymerization of butyl methacrylate in order to prepare glycosylated polymer particles. Core–shell particles consisting of a soft core of poly(butyl methacrylate) covered with glycopolymer bearing glucose moieties were obtained. Then these latex particles were employed to prepare polymer films with active surface. The surface bioactivity of this polymer coating was examined using the specific lectin Concanavalin A, Canavalia ensiformis. The specific and successful binding to the Concanavalin A was demonstrated by both fluorescence microscopy and spectroscopy being more intense with increasing concentration of block glycopolymer surfactant. The good accessibility of the glucose moieties at the surface of the coating makes this method a powerful tool to achieve potential materials for biomedical applications involving molecular recognition processes.

Self-assembly and drug delivery behaviors of a novel thermo-sensitive block glycopolymer

A novel thermo-sensitive block glycopolymer based on peracetylated maltoheptaose (AcMH) and poly(2-ethyl-2-oxazoline) (PEtOz) was synthesized for the first time and characterized by hydrogen nuclear magnetic resonance (1H NMR) spectroscopy and gel permeation chromatograph (GPC) analyses. To obtain such a block polymer, the dihydroxyl poly(2-ethyl-2-oxazoline) homopolymer (OH-PEtOz-OH) was first synthesized by cationic ring-opening polymerization of 2-ethyl-2-oxazoline (EtOz), and then coupled with the peracetylated maltoheptaose having a free hydroxyl group at the reducing end (AcMH-OH) prepared from β-cyclodextrin. It was found that the obtained block polymer could self-assemble into nanosize spherical micelles with a distinct core-shell structure in aqueous solution triggered by its amphiphilic character without any organic solvent. The model drug indomethacin (IND) was efficiently loaded into the resultant polymeric micelles, which was confirmed by 1H NMR spectra, transmission electron microscope (TEM) and dynamic light scattering (DLS) techniques. The release behavior of IND loaded micelles was well in response to the environmental temperature change. It is suggested that the resulting micelles might be a potential targeted carrier for drug delivery.

Well‐controlled amphiphilic block glycopolymers and their molecular recognition with lectins

AbstractThe atom transfer radical polymerization of an unprotected glycomonomer, 2‐{[(D‐glucosamin‐2N‐yl)carbonyl]oxy}ethyl methacrylate (HEMAGl) is firstly reported. Controlled polymerizations were performed with the CuBr/N,N,N′,N′,N′‐pentamethyldiethylene triamine catalytic system with ethyl 2‐bromoisobutyrate and 1,2‐bis(bromoisobutyryloxy) ethane as mono and difunctional initiators in DMF solutions (80% w/w) at 40 and 50 °C, respectively. The polymerization of HEMAGl resulted in a controlled polymerization with linear kinetics, molecular weights which increase with conversion and narrow polydispersity indexes. Mono and difunctional PHEMAGl macroinitiators were used to synthesize the amphiphilic di and triblock glycopolymers with n‐butyl acrylate, verifying their living character. The self‐assembly of these glycopolymers in distilled water and in 0.1M NaCl solutions was studied by dynamic light scattering, showing the role of hydrogen bonds and the hydrophobic parts. In addition, their interaction with Concanavalin A lectin was examined, demonstrating the influence of molecular weight and copolymer composition. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3623–3631, 2010

Well-defined pH-sensitive block glycopolymers via reversible addition-fragmentation chain transfer radical polymerization: Synthesis, characterization, and recognition with lectin

pH-Sensitive block glycopolymers of poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) and poly(3-O-methacryloy-α,β-D-glucopyranose) (PMAGlc) were synthesized via reversible addition–fragmentation chain transfer (RAFT) radical polymerization based on protected glycomonomer 3-O-methacryloyl-1,2:5,6-di-O-isopropylidene-D-glucofuranose (MAIpGlc). It was found that RAFT homopolymerization of MAIpGlc proceeded in a controlled fashion with 4-cyanopentanoic acid dithiobenzoate as chain transfer agent. Using the dithioester-capped PDEAEMA as macro-RAFT agent, block copolymerization of MAIpGlc was in good control as indicated by the linear pseudo first-order kinetic plot, the linear increment of number-average molecular weights as well as narrow and symmetrical gel permeation chromatography peaks, and low polydispersities. Well-defined diblock copolymers of DEAEMA and MAIpGlc were prepared successfully through the chain extension of PDEAEMA. The deprotection of MAIpGlc units in trifluoroacetic acid/H2O solution afforded PDEAEMA-b-PMAGlc block glycopolymer. The self-assembly behavior of PDEAEMA-b-PMAGlc in aqueous solution was investigated by using 1H NMR, UV-vis spectroscopy, dynamic light scattering, and transmission electron microscopy. The results demonstrated that spherical micelles with PDEAEMA as the hydrophobic cores and PMAGlc as the hydrophilic shells were formed in alkaline aqueous solution. These glucose-installed micelles had specific recognition with Concanavalin A. The combination of pH-sensitivity of PDEAEMA and biomolecular recognition of PMAGlc in one micellar system may create a multifunctional platform for targeted delivery, biomimetics, and biodection. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3350–3361, 2010

Controlled synthesis of linear and comb-like glycopolymers for preparation of honeycomb-patterned films

Honeycomb-patterned films can be facilely prepared by the breath figure method. However, it is still ambiguous how the polymer structure affects the morphologies of the films. In this work, poly(styrene- co-2-(2-,3-,4-,6-tetra- O-acetyl-β- d-glucosyloxy) ethyl methacrylate) (PS- co-AcGEMA) with well-defined linear and/or comb-like structures were synthesized by atom transfer radical polymerization (ATRP). These glycopolymers were used as precursors for the fabrication of pattern films by the breath figure method. The regularity and pore size of the films are greatly influenced by the polymer structure and the solution concentration. Highly ordered pattern films can be prepared from the comb-like glycopolymer and the linear block glycopolymers with relatively long PAcGEMA segment. Further studies of lectin recognition on the honeycomb-patterned films demonstrate that the glucose-containing films can specifically recognize Con A. These bioactive honeycomb-patterned films have potential applications as templates, picoliter beakers for bioanalysis and cell culture materials.

Synthesis of a family of amphiphilic glycopolymers via controlled ring-opening polymerization of functionalized cyclic carbonates and their application in drug delivery

Polymers bearing pendant carbohydrates have a variety of biomedical applications especially in the area of targeted drug delivery. Here we report the synthesis of a family of amphiphilic block glycopolymers containing d glucose, d galactose and d mannose via metal-free organocatalyzed ring-opening polymerization of functional cyclic carbonates generating narrowly dispersed products of controlled molecular weight and end-group fidelity, and their application in drug delivery. These glycopolymers self-assemble into micelles having a high density of sugar molecules in the shell, a size less than 100 nm with narrow size distribution even after drug loading, and little cytotoxicity, which are important for drug delivery. Using galactose-containing micelles as an example, we demonstrate their strong targeting ability towards ASGP-R positive HepG2 liver cancer cells in comparison with ASGP-R negative HEK293 cells although the galactose is attached to the carbonate monomer at 6-position. The enhanced uptake of DOX-loaded galactose-containing micelles by HepG2 cells significantly increases cytotoxicity of DOX as compared to HEK293. This new family of amphiphilic block glycopolymers has great potential as carriers for targeted drug delivery.