Mucin-like glycopolymer gels in electrosensory tissues generate cues which direct electrolocation in amphibians and neuronal activation in mammals

Mucin-like glycoproteins have established roles in epithelial boundary protection and lubricative roles in some tissues.This mini-review illustrates alternative functional roles which rely on keratan sulphate and sialic acid modifications to mucin glycopolymers which convey charge properties suggestive of novel electroconductive properties not previously ascribed to these polymers.Many tumour cells express mucin-like glycopolymers modified with highly sulphated keratan sulphate and sialic which can be detected using diagnostic biosensors.The mucin-like keratan sulphate glycopolymer present in the ampullae of lorenzini is a remarkable sensory polymer which elasmobranch fish(sharks,rays,skate) use to detect weak electrical fields emitted through muscular activity of prey fish.Information on the proton gradients is conveyed to neuromast cells located at the base of the ampullae and mechanotransduced to neural networks.This ampullae keratan sulphate sensory gel is the most sensitive proton gradient detection polymer known in nature.This process is known as electrolocation,and allows the visualization of prey fish under conditions of low visibility.The bony fish have similar electroreceptors located along their lateral lines which consist of neuromast cells containing sensory hairs located within a cupula which contains a sensory gel polymer which detects distortions in fluid flow in channels within the lateral lines and signals are sent back to neural networks providing information on the environment around these fish.One species of dolphin,the Guiana dolphin,has electrosensory pits in its bill with similar roles to the ampullae but which have evolved from its vibrissal system.Only two terrestrial animals can undertake electrolocation,these are the Duck-billed platypus and long and short nosed Echidna.In this case the electrosensor is a highly evolved innervated mucous gland.The platypus has 40,000 electroreceptors around its bill through which it electrolocates food species.The platypus has poor eyesight,is a nocturnal feeder and closes its eyes,nostrils and ears when it hunts,so electrolocation is an essential sensory skill.Mammals also have sensory cells containing stereocilia which are important in audition in the organ of corti of the cochlea and in olfaction in the olfactory epithelium.The rods and cones of the retina also have an internal connecting cilium with roles in the transport of phototransduced chemical signals and activation of neurotransmitter release to the optic nerve.Mucin-like glycopolymer gels surround the stereocilia of these sensory hair cells but these are relatively poorly characterized however they deserve detailed characterization since they may have important functional attributes.

MORPHOLOGICAL TRANSITION BETWEEN VESICLES AND TUBULES FOR A GLYCOPOLYMER-CONTAINING AMPHIPHILIC DIBLOCK COPOLYMER IN AQUEOUS SOLUTIONS

The morphological transition of molecular assemblies in aqueous solutions for a new amphiphilic diblock copolymer induced by changing the initial solvent conditions was studied by transmission electron microscopy (TEM). The copolymer was polystyrene(77)-b-poly[2-(beta -D-glucopyranosyloxy)ethyl acrylate (6)] (PSt(77)-b-PGEA(6)) and the solvent was a mixture of DMF and THF. PSt(77)-b-PGEA(6) yields vesicles and tubules when it is initially dissolved in THF and DMF respectively. The morphological transition between vesicles and tubules can be achieved by simply varying the amounts of THF and DMF, or changing the temperature at which the aggregates were prepared.

Glycopolymer N-halamine-modified biochars with high specificity for Escherichia coli eradication

Antibiotic-resistant bacteria contamination in environments imposes great threats to human life health.This research aims to develop novel targeted antibacterial biochars for achieving high selectivity to kill pathogenic Escherichia coli(E.coli).The glycopolymer N-halamine-modified biochars(i.e.,BCPMA-Cl)were synthesized by the modification of biochars with poly[2-(methacrylamido)glucopyranose-coacrylamide](P(MAG-co-AM),followed by chlorination treatment.Based on the results of FTIR,turbidity,XPS,and UV–vis,BCPMA-Cl was successfully synthesized and demonstrated to be able to eliminate Staphylococcus aureus(S.aureus)and E.coli.Especially,BCPMA-Cl possessed extremely potent to specific-killing 10^(4) CFU·ml^(-1) of E.coli with lower hemolytic activity(<5%).Additionally,the antibacterial mechanisms of BCPMA-Cl against bacteria were contact-killing and release-killing contributed by active chlorine(i.e.,Cl^(+)).Therefore,this work provided a cost-effective and facile approach for preparation of functional biochars used for bacteria-specific therapeutic applications via livestock pollutants as well as showing a promising strategy to avoid bacterial resistance.

Synthesis of Thermoresponsive Poly( diethyleneglycol methacrylate-co-6-Ovinyladipoyl-D-glucopyranose) Glycopolymer via RAFT Polymerization

The monomer 6-O-vinyladipoyl-D-glucopyranose( VAG)was synthesized by lipase catalyzed trans-esterification of divinyladipate with D-glucopyranose. A novel double hydrophilic glycopolymer poly( diethyleneglycol methacrylate-co-6-Ovinyladipoyl-D-glucopyranose)( P( DEGMA-co-VAG)) with narrow polydispersity( PDI) and thermosensitivity was prepared by reversible addition-fragmentation chain transfer( RAFT)polymerization. P( DEGMA-co-VAG) was characterized by1 H NMR,FTIR and gel permeation chromatography( GPC). The characterization of UV-visible spectroscopy showed that the micelles from glycopolymer P( DEGMA-co-VAG) were thermo-responsive and the low critical solution temperature( LCST) could be controlled by the molar ratio of monomers. When the molar ratio of DEGMA and VAG was 2∶ 1,the LCST of P( DEGMA-co-VAG) was36 ℃ in aqueous solution,which could form nano micelles in the human body environment. It was found that P( DEGMA-co-VAG)was non-toxic at 0. 1-1 mg / m L concentrations when incubated with pig iliac endothelial cells( PIECs) for 24 h. Thus,the synthesized glycopolymers has great potential as drug delivery carriers.

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.

Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy

Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their application.To address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor effect.In this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into mB4S.After internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP secretion.Meanwhile,diABZI effectively activated the STING pathway.Treatment with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

Chemical Synthesis of Globo H and Mannobiose Glycopolymers and their Immunological Stimulation

Tumor-associated carbohydrate antigens(TACAs)provide a special class of tumor-specific antigens that show promising applications in cancer immunotherapy.However,the weak immunogenicity and structural complexity of TACAs are obstacles to their clinical application.Here,based on a fast and low-cost purification strategy for oligosaccharide synthesis,the synthesis of tumour-associated carbohydrate antigens Globo H and mannobiose which resembles repeat unit of mannan was achieved.To enhance the immunogenicity and multivalent effect,Globo H and mannobiose were covalently attached to degradable polymer backbones.2D spindle-like lamellar micelle and globular micelle were obtained from glycopolymer through a solvent-exchange method of self-assembly.The glyconanoparticle showed good biocompatibility and degradability.Immunological functions of these glyconanoparticles such as stimulation of BMDC to cause upregulation of inflammatory factors were preliminarily explored.

Cathepsin B-responsive and gadolinium-labeled branched glycopolymer-PTX conjugate-derived nanotheranostics for cancer treatment

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer.Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment.A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate,conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a(Ppa)with a branched glycopolymer.The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B,and PTX was simultaneously released to exert its therapeutic effect.The theranostic nanomedicine,branched glycopolymer-PTX-DOTA-Gd,had an extended circulation time,enhanced accumulation in tumors,and excellent biocompatibility with significantly reduced gadolinium ion(Gd3+)retention after 96 h post-injection.Enhanced imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90%were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic toxicity.This branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer.

The glyco-regioisomerism effect on dynamic interactions between glycopolymers with galactose pendants and benzoxaborole-containing polymer

This work investigated the effect of glyco-regioisomerism of glycopolymers on their dynamic interaction with benzoxaborole-containing polymers. Two kinds of glycopolymers, P-1-Gal and P-6-Gal, i.e. galactoside pendant group linked to the identical main chain through its anomeric(C1) and C6-hydroxyl group position, respectively, were studied. We found that P-6-Gal showed stronger binding strength to the PNIPAM-co-PBOB polymer than P-1-Gal did, which controlled the macroscopic property of the resultant hydrogels at a molecular level.

INTERACTION BETWEEN THE SURFACE GLYCOSYLATED POLYPROPYLENE MEMBRANE AND LECTIN

A glycopolymer bearing glucose residues was tethered onto the surface of polypropylene microporous membrane by UV-induced graft polymerization ofα-allyl glucoside.Concanavalin A (Con A),a glucose recognizing lectin,could be specifically adsorbed to the membrane surface.On the other hand,the membrane surface showed no recognition ability to another lectin peanut agglutinin.Moreover,the recognition complex between the glycosylated membrane surface and Con A could be inhibited by glucose and mannose solution.T...

Modification of polyfluorene nanoparticles via inclusion complexa- tion based on cyclodextrin for lectin sensing and cell imaging

Currently, conjugated polymer nanoparticles are widely used with many biological applications, especially bio-imaging and labeling. Thus their modification with different biomacromolecules becomes a crucial step before various applications. In literature,this modification was normally performed via covalent bonds. To our best knowledge, modification based on inclusion complexation has not been reported. Herein, via host-guest interaction between cyclodextrin and adamantane, supramolecular modification to conjugated polyfluorene nanoparticles has been successfully achieved. The glycopolymer-modified conjugated polymer nanoparticles showed excellent binding ability to lectins, such as Galectin-3 and selective imaging behavior to Hep G2 cells.

Carboxymethyl glycoside lactone(CMGL) synthons:Scope of the method and preliminary results on step growth polymerization of α-azide-ω-alkyne glycomonomers

Carboxymethyl glycoside lactones(CMGLs) are bicyclic synthons which open readily for accessing new types of pseudo-glycoconjugates,such as sugar-amino acid hybrids,neoglycolipids,pseudodisaccharides,and membrane imaging systems.After lactone opening,free OH-2 is available for further functionalization,leading to 1,2-bisfunctionalized derivatives.This strategy is illustrated herein with new polymerizable systems of the AB type bearing both azide and alkyne functions prepared from α or β gluco-CMGL synthons.After the reaction of lactones with propargylamine,an azido group was introduced by two different sequences leading to either the 2-manno-azido or the 6-gluco-azido products.The capability of these AB monomers to undergo step growth polymerization through copper(I) catalyzed alkyne-azide cycloaddition(CuAAC) and generate glycopolytriazoles was evidenced.

One-pot synthesis of hyperbranched poly(amido amine) clicked with a sugar shell via Michael addition polymerization and thiol click reaction

This paper reports the production of glycopolymers via a simple and flexible method.A novel glycopolymer with a hyperbranched poly(amido amine) core and a sugar shell (HPAA-GLc) was synthesized by using thiol-ene click reaction via facile one-pot method.Hyperbranched poly(amido amine) with vinyl terminals was first synthesized by Michael addition polymerization of N,N'-methylene bisacrylamide (MBA) with 1-(2-aminoethyl) piperazine (AEPZ).Subsequently,thiol-ene click reaction between vinyl units of hyperbranched poly(amido amine) and thio-glucose was performed in situ.Based on the NMR result,all the vinyl groups reacted with thiol-glucose in 120 min.Strong photoluminescence emission was observed from the aqueous solution of HPAA-GLc.

Dendritic cells maturation facilitated by group-adjustable lipopolysaccharide analogues synthesized via RAFT polymerization

Transforming immature DCs into mature state to activate cellular immunity is a critical step in initiating immunoprophylaxis and immunotherapy.Lipopolysaccharides(LPS)can promote DCs maturation by binding receptor on DCs surface,but their clinical application is limited due to biological toxicity.Although many LPS analogues have been developed,complex synthesis and purification hinder their practical application.Here,we propose a novel and simple strategy to synthesize LPS analogues with adjustable structural units.Using monomer units similar to the key functional groups of LPS,we synthesize LPS analogues with different group ratios by RAFT polymerization.The obtained analogues have little negative effect on cell viability.Compared with LPS,the analogues show greater promoting effect on DCs maturation.And the analogues can be applied to different scenarios since the degrees of promoting DCs maturation by LPS analogues with different group ratios are different.This strategy provides a new direction for synthesizing LPS analogues,and it has the potential to produce LPS analogues on a large scale with tunable promoting DCs maturation effect.

A facile approach to prepare hybrid nanoparticles with morphology controlled by the thickness of glyco-shell

Herein, we designed a novel amphiphilic triblock glycopolymer poly（oligo（ethyleneglycol） methacry- late）-block-poly（maltopyranoside methacrylate）-block-polystyrene （POMA-b-PMal-b-PS） via the com- bination of reversible addition-fragmentation chain transfer （RAFT） polymerization and post- polymerization modification. The micelles with core-shell-corona structures were prepared by direct self-assembly of this glycopolymer in water. We found that these micelles can be used in in situ formation and stabilization of AuNPs. By controlling the thickness of glyco-shell, we successfully obtained lanus particles and raspberry-like particles with AuNPs in the sugar shell.