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This article describes the design, synthesis, and folding behaviors of β‐1,2‐linked glycopolymers as a bioconjugate‐based foldamer. The synthesis of alkyne‐containing β‐glycosyl azides has been achieved via anomeric substitution using tetrabutylammonium azide (Bu4NN3) to 1,2‐anhydro sugar and subsequent esterification with 5‐hexynoic acid. Copper‐catalyzed alkyne‐azide 1,3‐dipolar cycloaddition of the glycosyl azide leads to the formation of β‐1,2‐linked glycopolymer alternating 4‐triazolyl butanoate and tribenzylated d‐galactose (PolyGal) or d‐glucose unit (PolyGlu). The folding and chiroptical properties of the polymers are discussed through UV–vis and CD spectroscopy and anisotropic factors of CD (gCD) values. The results suggest that PolyGal would adopt a helically folded structure in ClCH2CH2Cl (DCE) or THF. Thermal stability of the folded structure of PolyGal in less polar DCE appears to increase compared with that in THF. It is found that the folded structure of PolyGal in THF denatures to a random coil above 40°C. It is indicated that PolyGlu can possibly form the helically folded structure in DCE and adopt a random coil structure at high temperature region. In polar THF, PolyGlu does not fold the conformation at all the observed temperature region. Such phenomena suggest a special role of stereochemistry at the 4 position on the folding behaviors. [ABSTRACT FROM AUTHOR]

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.

In the development of dendritic cell (DC) vaccines, the maturation of DCs is a critical stage. Adjuvants play a pivotal role in the maturation of DCs, with a major concern being to ensure both efficacy and safety. This study introduces an innovative approach that combines high efficacy with safety through the synthesis of micro‐adjuvants grafted with copolymers of 2‐(methacrylamido) glucopyranose (MAG) and methacryloxyethyl trimethyl ammonium chloride (DMC). The utilization of metal‐free surface‐initiated atom transfer radical polymerization enables the production of safe and recyclable adjuvants. These micrometer‐sized adjuvants surpass the optimal size range for cellular endocytosis, enabling the retrieval and reuse of them during the ex vivo maturation process, mitigating potential toxicity concerns associated with the endocytosis of non‐metabolized nanoparticles. Additionally, the adjuvants exhibit a "micro‐ligand‐mediated maturation enhancement" effect for DC maturation. This effect is influenced by the shape of the particle, as evidenced by the distinct promotion effects of rod‐like and spherical micro‐adjuvants with comparable sizes. Furthermore, the porous structure of the adjuvants enables them to function as cargo‐carrying "micro‐shuttles", releasing antigens upon binding to DCs to facilitate efficient antigen delivery. [ABSTRACT FROM AUTHOR]

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. A branched glycopolymer-EPI prodrug-derived nanoassembly combined with a STING agonist to remodel an immunosuppressive microenvironment to an immuno-supportive one, thus potentiating the therapy effect of anti-PD-L1 antibodies. [Display omitted] [ABSTRACT FROM AUTHOR]

Glycopolymers are functional polymers with saccharide moieties on their side chains and are attractive candidates for biomaterials. Postpolymerization modification can be employed for the synthesis of glycopolymers. Activated esters are useful in various fields, including polymer chemistry and biochemistry, because of their high reactivity and ease of reaction. In particular, the formation of amide bonds caused by the reaction of activated esters with amino groups is of high synthetic chemical value owing to its high selectivity. It has been employed in the synthesis of various functional polymers, including glycopolymers. This paper reviews the recent advances in polymers bearing activated esters for the synthesis of glycopolymers by postpolymerization modification. The development of polymers bearing hydrophobic and hydrophilic activated esters is described. Although water-soluble activated esters are generally unstable and hydrolyzed in water, novel polymer backbones bearing water-soluble activated esters are stable and useful for postpolymerization modification for synthesizing glycopolymers in water. Dual postpolymerization modification can be employed to modify polymer side chains using two different molecules. Thiolactone and glycine propargyl esters on the polymer backbone are described as activated esters for dual postpolymerization modification. [ABSTRACT FROM AUTHOR]

Investigation of polymeric conformations in different solvents is critical because block copolymer solution morphology is not only associated with the architecture but also with its characteristic features which depend upon the solvent polarity. A series of double hydrophobic diblock copolymers comprising polyisobutylene (PIB) segment and varying sugar pendant units have been prepared by a combination of living cationic and reversible addition-fragmentation chain transfer (RAFT) polymerizations. After the deprotection of the acetate from sugar pendants, the synthesized water-soluble amphiphilic block copolymers showed morphological transformations in both aqueous and organic media. A conformational transition due to a change in solvent polarity from polar protic to nonpolar was supported by 1H NMR spectroscopy. The dynamic light scattering (DLS) experiments demonstrated that the hydrodynamic diameters of aggregates varied with solvent polarity. Field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) evidenced the morphological changes from micellar to tubular orientation. Finally, the self-assembly behavior of PIB-based glycopolymers due to changes in solvent polarity is proposed. [ABSTRACT FROM AUTHOR]

Glycopolymers are functional polymers with saccharide moieties on their side chains and are attractive candidates for biomaterials. Postpolymerization modification can be employed for the synthesis of glycopolymers. Activated esters are useful in various fields, including polymer chemistry and biochemistry, because of their high reactivity and ease of reaction. In particular, the formation of amide bonds caused by the reaction of activated esters with amino groups is of high synthetic chemical value owing to its high selectivity. It has been employed in the synthesis of various functional polymers, including glycopolymers. This paper reviews the recent advances in polymers bearing activated esters for the synthesis of glycopolymers by postpolymerization modification. The development of polymers bearing hydrophobic and hydrophilic activated esters is described. Although water-soluble activated esters are generally unstable and hydrolyzed in water, novel polymer backbones bearing water-soluble activated esters are stable and useful for postpolymerization modification for synthesizing glycopolymers in water. Dual postpolymerization modification can be employed to modify polymer side chains using two different molecules. Thiolactone and glycine propargyl esters on the polymer backbone are described as activated esters for dual postpolymerization modification.

Sensing of lectins are utmost necessary for its inflammatory, digestive disorder, gut pains and toxicity to human beings and for this purpose we have chosen polythiophene (PT) for its exciting optoelectronic properties. Because of precise carbohydrate specificities of lectin and to make PT water soluble for sensing of lectin, we have synthesized polythiophene-g-poly(N,N-dimethylaminoethyl methacrylate) -co-poly(glucose-hydroxyethyl methacrylate) (PT-g-pDMAEMA-co-pGLU-HEM), [PTDG]) from polythiophene macroinitiator (PTI) by copolymerizing DMAEMA and GLU-HEM monomers mixture with CuCl/HMTETA catalyst/ligand followed by hydrolysis using alcoholic NaOMe solution. The Mn of PTI was 38000, polydispersity 2.5, head-tail (H-T) regioregularity 70 mol % and Mn of unhydrolyzed PTDG is 98,900. The UV-Vis spectra of PTDG solution shows two absorption peaks at 430 and 462 nm but it shows a sharp emission peak at 544 nm which quenches with increasing pH. Concanavalin A (ConA) shows an absorbance peak at 278 nm and with addition of PTDG solution absorbance intensity increases showing hypochromic effect. Benesi–Hildebrand plot of reciprocal molar extinction coefficients with concentration suggests 1:1 complex formation between PTDG and ConA. With addition of ConA fluorescence quenching of PTDG solution occurred and using the fluorescence intensity ratio vs concentration plot the limit of detection (LOD) of Con A lectin is found to be 57 µg/L and storing the polymer solution for two months exhibits good durability. The morphology of PTDG changes from vesicle to compound micellar aggregate on addition of Con A lectin. We have synthesized a polythiophene glcopolymer (PT-g-pDMAEMA-co-pGLU-HEM), PTDG) using ATRP technique and its UV-Vis and fluorescence spectra indicates pH responsivity and lectin sensing property with LOD of 57 µg/L. [ABSTRACT FROM AUTHOR]

IgA nephropathy (IgAN) is the most common glomerular autoimmune disease and has severe long‐term consequences for patients, with 40% of the patients eventually progressing to end‐stage renal disease. Despite the severity, no causal treatment is currently available. While the pathogenesis of IgAN is complex, disease severity is linked to autoantibodies against the gd‐IgA1 epitope, a stretch in the hinge region of IgA1 that lacks O‐glycans and is found in the characteristic immune complexes deposited in the kidneys of IgAN patients. One elegant, causal approach would be to remove the anti‐gd‐IgA1 autoantibodies and consequently reduce the immune complex burden on the kidneys. The administration of synthetic polymers that present autoantigens in a multivalent manner have been established as promising therapeutic strategies in other autoimmune diseases and may be applied to IgAN. We here present an improved protocol for the synthesis of the gd‐IgA1 epitope, its successful coupling to a poly‐L‐lysine polymer and proof‐of‐concept experiments that the polymer‐bound synthetic glycopeptide is able to capture the IgAN autoantibodies, making this approach a promising way forward for developing a targeted treatment option for IgAN patients. [ABSTRACT FROM AUTHOR]

A simple and cost-effective method for the fabrication of a safe, dual-responsive, highly stretchable, self-healing and injectable hydrogel is reported based on a combination of dynamic boronate ester bonds and hydrogen bonding interactions. The mechanical properties of the hydrogel are tunable by adjusting the molar ratios between sugar moieties on the polymer and borax. It was remarkable to note that the 2:1 ratio of sugar and borate ion significantly improves the mechanical strength of the hydrogel. The injectability, self-healing and stretchability properties of the hydrogel were also examined. In addition, the impact of the variation of the pH and the addition of free sugar responsiveness of the hydrogel was studied. High MRC-5 cell viability was noticed by the 3D live/dead assay after 24 h cell culture within the hydrogel scaffold. Hence, the developed hydrogels have desirable features that warrant their applications for drug delivery, scaffolds for cell and tissue engineering. [ABSTRACT FROM AUTHOR]

Microgels acts as a potential candidate for responsive composite materials, which has been favored by scientists because of its excellent colloid stability, easy integration, and most of their surface area can be used as support after modification. Specififically, microgels are fascinating capable of maintaining good biocompatibility and controlled-release in vivo and making the possible for applications in biomaterials and biomedicines. Besides, in the process of microgel synthesis, some targeting factors can be combined to achieve the purpose of cell targeting and uptake. Therefore, how to fundamentally design microgels is an urgent problem to be solved. In this study, we design and synthesize an injectable microgel P(DEGMA- co -OVNGal) that is made of 2-methyl-2-acrylate-2-(2-methoxy ethoxy) ethyl ester (DEGMA) and glycopolymer (OVNGal) that is thermoresponsive and contains galactose. When the content of crosslinking agent is regulated, the microgel will realize the transformation from sol to gel at the temperature around human body, causing the controlled release of the loaded drugs. With the increase of crosslinker content from 1% to 7%, the appearance of microgel changed from loose and ordered to compact and hard morphology, the swelling ratio of microgel decreased from 187% to 142%, and the phase volume transition temperature decreased from 29.2°C to 28°C. The results indicated that when the monomer ratio (DEGMA: OVNGal) increased from 2:1 to 40:1 with the amount of crosslinking agent at 1%, the particle size of microgel increased from 460 nm to 660 nm. In vitro released studies confirmed that the cumulative released DOX (doxorubicin, as a selected model drug) from the microgel can reach 50% after 7 days. Furthermore, in vitro experiments demonstrated that the injectable microgel P(DEGMA- co -OVNGal) can target HepG2 cells effectively and meantime dispalys excellent biocompatibility. Therefore, the injected microgels based on P(DEGMA- co -OVNGal) have the potential to serve as a robust and promising drug delivery carrier for targeted cancer therapy. Graphical Abstract [ABSTRACT FROM AUTHOR]

In this work, we designed biodegradable glycopolymers consisting of a carbohydrate conjugated to a biodegradable polymer, poly(lactic acid) (PLA), through a poly(ethylene glycol) (PEG) linker. The glycopolymers were synthesized by coupling alkyne end-functionalized PEG-PLA with azide-derivatized mannose, trehalose, or maltoheptaose via the click reaction. The coupling yield was in the range of 40–50% and was independent of the size of the carbohydrate. The resulting glycopolymers were able to form micelles with the hydrophobic PLA in the core and the carbohydrates on the surface, as confirmed by binding with the lectin Concanavalin A. The glycomicelles were ~30 nm in diameter with low size dispersity. The glycomicelles were able to encapsulate both non-polar (rifampicin) and polar (ciprofloxacin) antibiotics. Rifampicin-encapsulated micelles were much smaller (27–32 nm) compared to the ciprofloxacin-encapsulated micelles (~417 nm). Moreover, more rifampicin was loaded into the glycomicelles (66–80 μg/mg, 7–8%) than ciprofloxacin (1.2–2.5 μg/mg, 0.1–0.2%). Despite the low loading, the antibiotic-encapsulated glycomicelles were at least as active or 2–4 times more active than the free antibiotics. For glycopolymers without the PEG linker, the antibiotics encapsulated in micelles were 2–6 times worse than the free antibiotics. [ABSTRACT FROM AUTHOR]

Non-fouling polymers are effective in improving the pharmacokinetics of therapeutic proteins, but short of biological functions for tumor targeting. In contrast, glycopolymers are biologically active, but usually have poor pharmacokinetics. To address this dilemma, herein we report in situ growth of glucose- and oligo(ethylene glycol)-containing copolymers at the C-terminal site of interferon alpha, an antitumor and antivirus biological drug, to generate C-terminal interferon alpha-glycopolymer conjugates with tunable glucose contents. The in vitro activity and in vivo circulatory half-life of these conjugates were found to decrease with the increase of glucose content, which can be ascribed to complement activation by the glycopolymers. Additionally, the cancer cell endocytosis of the conjugates was observed to maximize at a critical glucose content due to the tradeoff between complement activation and glucose transporter recognition by the glycopolymers. As a result, in mice bearing ovarian cancers with overexpressed glucose transporter 1, the conjugates with optimized glucose contents were identified to possess improved cancer-targeting ability, enhanced anticancer immunity and efficacy, and increased animal survival rate. These findings provided a promising strategy for screening protein-glycopolymer conjugates with optimized glucose contents for selective cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Diseases induced by bacterial and viral infections are common occurrences in our daily life, and the main prevention and treatment strategies are vaccination and taking antibacterial/antiviral drugs. However, vaccines can only be used for specific viral infections, and the abuse of antibacterial/antiviral drugs will create multi−drug−resistant bacteria and viruses. Therefore, it is necessary to develop more targeted prevention and treatment methods against bacteria and viruses. Proteins on the surface of bacteria and viruses can specifically bind to sugar, so glycopolymers can be used as potential antibacterial and antiviral drugs. In this review, the research of glycopolymers for bacterial/viral detection/inhibition and antibacterial/antiviral applications in recent years are summarized. [ABSTRACT FROM AUTHOR]

The emergence and growth of bacterial resistance to antibiotics poses an enormous threat to humanity in the future. In this regard, the discovery of new antibiotics and the improvement of existing ones is a priority task. In this study, we proposed the synthesis of new polymeric conjugates of polymyxin B, which is a clinically approved but limited-use peptide antibiotic. In particular, three carboxylate-bearing polymers and one synthetic glycopolymer were selected for conjugation with polymyxin B (PMX B), namely, poly(α,L-glutamic acid) (PGlu), copolymer of L-glutamic acid and L-phenylalanine (P(Glu-co-Phe)), copolymer of N-vinyl succinamic acid and N-vinylsuccinimide (P(VSAA-co-VSI)), and poly(2-deoxy-2-methacrylamido-D-glucose) (PMAG). Unlike PGlu and PMAG, P(Glu-co-Phe) and P(VSAA-co-VSI) are amphiphilic and form nanoparticles in aqueous media. A number of conjugates with different polymyxin B loading were synthesized and characterized. In addition, the complex conjugates of PGLu or PMAG with polymyxin B and deferoxamine (siderophore) were obtained. A release of PMX B from Schiff base and amide-linked polymer conjugates was studied in model buffer media with pH 7.4 and 5.8. In both cases, a more pronounced release was observed under slightly acidic conditions. The cytotoxicity of free polymers and PMX B as well as their conjugates was examined in human embryonic kidney cells (HEK 293T cell line). All conjugates demonstrated reduced cytotoxicity compared to the free antibiotic. Finally, the antimicrobial efficacy of the conjugates against Pseudomonas aeruginosa was determined and compared. The lowest values of minimum inhibitory concentrations (MIC) were observed for polymyxin B and polymyxin B/deferoxamine conjugated with PMAG. Among the polymers tested, PMAG appears to be the most promising carrier for delivery of PMX B in conjugated form due to the good preservation of the antimicrobial properties of PMX B and the ability of controlled drug release. [ABSTRACT FROM AUTHOR]

A simple environment-friendly system is attractive for synthesizing functional polymer materials, including glycopolymers. Herein, we successfully synthesized glycopolymers via an aqueous one-pot and open-air system combined with photoinduced electron/energy transfer-reversible addition-fragmentation chain-transfer (PET-RAFT) polymerization using a novel water-soluble monomer having an activated ester, followed by modification with amine-containing saccharide derivatives in water at room temperature. [ABSTRACT FROM AUTHOR]

Development of fluorescent imaging probes is an important topic of research for the early diagnosis of cancer. Based on the difference between the cellular environment of tumor cells and normal cells, several "smart" fluorescent probes have been developed. In this work, a glycopolymer functionalized Förster resonance energy transfer (FRET) based fluorescent sensor is developed, which can monitor the pH change in cellular system. One‐pot sequential reversible addition‐fragmentation chain transfer (RAFT)polymerization technique is employed to synthesize fluorescent active triblock glycopolymer that can undergo FRET change on the variation of pH. A FRET pair, fluorescein o‐acrylate (FA) and 7‐amino‐4‐methylcoumarin (AMC) is linked via a pH‐responsive polymer poly [2‐(diisopropylamino)ethyl methacrylate] (PDPAEMA), which can undergo reversible swelling/deswelling under acidic/neutral condition. The presence of glycopolymer segment provides stability, water solubility, and specificity toward cancer cells. The cellular FRET experiments on cancer cells (MDA MB 231) and normal cells (3T3 fibroblast cells) demonstrate that the material is capable of distinguishing cells as a function of pH change. [ABSTRACT FROM AUTHOR]

Trehalose is a well-known preservation agent for various biomolecules, but the mechanism by which it achieves this function remains unclear. Trehalose glycopolymers with various sugar densities were utilized for affinity analysis and preservation assays with α-amylase. Strong affinity and weak preservation ability were observed when glycopolymers with excess sugar density were applied. In contrast, weak affinity and strong preservation abilities were observed when glycopolymers featuring appropriate sugar densities were used. These results indicated that the affinity was not correlated with preservation ability under heated conditions. It was important for the trehalose glycopolymer to form a densely packed trehalose glycocluster, regardless of affinity, to achieve preferable preservation properties. [ABSTRACT FROM AUTHOR]

Codelivery of chemotherapeutics via nanomaterials has attracted much attention over the last decades due to improved drug delivery to tumor tissues, decreased systemic effects, and increased therapeutic efficacies. High porosities, large pore volumes and surface areas, and tunable structures have positioned metal–organic frameworks (MOFs) as promising drug delivery systems (DDSs). In particular, nanoscale Zr-linked MOFs such as MOF-808 offer notable advantages for biomedical applications such as high porosity, good stability, and biocompatibility. In this study, we report efficient dual drug delivery of floxuridine (FUDR) and carboplatin (CARB) loaded in MOF-808 nanoparticles to cancer cells. The nanoparticles were further functionalized by a poly-(acrylic acid-mannose acrylamide) (PAAMAM) glycopolymer coating to obtain a highly selective DDS in cancer cells and enhance the therapeutic efficacy of chemotherapy. While MOF-808 was found to enhance the individual therapeutic effects of FUDR and CARB toward cancerous cells, combining FUDR and CARB was seen to cause a synergistic effect, further enhancing the cytotoxicity of the free drugs. Enhancement of CARB loading and therefore cytotoxicity of the CARB-loaded MOFs could be induced through a modified activation protocol, while coating of MOF-808 with the PAAMAM glycopolymer increased the uptake of the nanoparticles in cancer cells used in the study and offered a particularly significant selective drug delivery with high cytotoxicity in HepG2 human hepatocellular carcinoma cells. These results show how the enhancement of cytotoxicity is possible through both nanovector delivery and synergistic treatment, and that MOF-808 is a viable candidate for future drug delivery studies. [ABSTRACT FROM AUTHOR]

Glycopolymer materials have emerged as a significant biopolymer class that has piqued the scientific community's attention due to their potential applications. Recently, they have been found to be a unique synthetic biomaterial; glycopolymer materials have also been used for various applications, including direct therapeutic methods, medical adhesives, drug/gene delivery systems, and biosensor applications. Therefore, for the next stage of biomaterial research, it is essential to understand current breakthroughs in glycopolymer-based materials research. This review discusses the most widely utilized synthetic methodologies for glycopolymer-based materials, their properties based on structure–function interactions, and the significance of these materials in biosensing applications, among other topics. When creating glycopolymer materials, contemporary polymerization methods allow precise control over molecular weight, molecular weight distribution, chemical activity, and polymer architecture. This review concludes with a discussion of the challenges and complexities of glycopolymer-based biosensors, in addition to their potential applications in the future. [ABSTRACT FROM AUTHOR]

The cellular glycocalyx is involved in diverse biological phenomena in health and disease. Yet, molecular level studies have been challenged by a lack of tools to precisely manipulate this heterogeneous structure. Engineering of the cell surface using insertion of hydrophobic-terminal materials has emerged as a simple and efficient method with great promise for glycocalyx studies. However, there is a dearth of information about how the structure of the material affects membrane insertion efficiency and resulting density, the residence time of the material, or what types of cells can be utilized. Here, we examine a panel of synthetic mucin structures terminated in highly efficient cholesterylamide membrane anchors for their ability to engineer the glycocalyx of five different cell lines. We examined surface density, residence time and half-life, cytotoxicity, and the ability be passed to daughter cells. We report that this method is robust for a variety of polymeric structures, long-lasting, and well-tolerated by a variety of cell lines.

The high level of accumulation of therapeutic agents in tumors is crucial for cancer treatment. Compared to the passive tumor-targeting effect, active tumor-targeting delivery systems, primarily mediated by peptides with high production costs and reduced circulation time, are highly desired. Platelet-driven technologies have opened new avenues for targeted drug delivery prevalently through a membrane coating strategy that involves intricate manufacturing procedures or the fucoidan-mediated hitchhiking method with limited platelet affinity. Here, a novel type of amphiphilic glycopolymer self-assembled micellar nanoparticle has been developed to adhere to naturally activated platelets in the blood. The simultaneous integration of fucose and sialic acid segments into glycopolymers enables closer mimicry of the structure of P-selectin glycoprotein ligand-1 (PSGL-1), thereby increasing the affinity for activated platelets. It results in the formation of glycopolymeric micelle-platelet hybrids, facilitating targeted drug delivery to tumors. The selective platelet-assisted cellular uptake of docetaxel (DTX)-loaded glycopolymeric micelles leads to lower IC 50 values against 4T1 cells than that of free DTX. The directed tumor-targeting effect of activated platelets has significantly improved the tumor accumulation capacity of the glycopolymeric nanoparticles, with up to 21.0% found in tumors within the initial 0.2 h. Additionally, with acid-responsive drug release and inherent antimetastasis properties, the glycopolymeric nanoparticles ensured potent therapeutic efficacy, prolonged survival time, and reduced cardiotoxicity, presenting a new and unexplored strategy for platelet-directed drug delivery to tumors, showing promising prospects in treating localized tumors and preventing tumor metastasis.

Designing surfaces that enable controlled presentation of multivalent ligand clusters (e.g., for rapid screening of biomolecular binding constants or design of artificial extracellular matrices) is a cross-cutting challenge in materials and interfacial chemistry. Existing approaches frequently rely on complex building blocks or scaffolds and are often specific to individual substrate chemistries. Thus, an interlayer chemistry that enabled efficient nanometer-scale patterning on a transferrable layer and subsequent integration with other classes of materials could substantially broaden the scope of surfaces available for sensors and wearable electronics. Recently, we have shown that it is possible to assemble nanometer-resolution chemical patterns on substrates including graphite, use diacetylene polymerization to lock the molecular pattern together, and then covalently transfer the pattern to amorphous materials (e.g., polydimethylsiloxane, PDMS), which would not natively enable high degrees of control over ligand presentation. Here, we develop a low-viscosity PDMS formulation that generates very thin films (<10 μm) with dense cross-linking, enabling high-efficiency surface functionalization with polydiacetylene arrays displaying carbohydrates and other functional groups (up to 10-fold greater than other soft materials we have used previously) on very thin films that can be integrated with other materials (e.g., glass and soft materials) to enable a highly controlled multivalent ligand display. We use swelling and other characterization methods to relate surface functionalization efficiency to the average distance between cross-links in the PDMS, developing design principles that can be used to create even thinner transfer layers. In the context of this work, we apply this approach using precision glycopolymers presenting structured arrays of N -acetyl glucosamine ligands for lectin binding assays. More broadly, this interlayer approach lays groundwork for designing surface layers for the presentation of ligand clusters on soft materials for applications including wearable electronics and artificial extracellular matrix.

Weak binding of carbohydrates with protein receptors possesses serious drawbacks in the advancement of therapeutics; however, the development of strategies for multipoint interactions between carbohydrates and protein can overcome these challenges. One such method is developed in this work where glycopolymer- grafted silica nanoparticles with a large number of carbohydrate units are prepared for the interactions with multiple binding sites of the protein. First, a glycomonomer, β-d-galactose-hydroxyethyl methacrylate (β-GEMA), was synthesized in a two-step process by coupling β-d-galactose pentaacetate and hydroxyethyl methacrylate (HEMA), followed by deacetylation for the preparation of poly(β-GEMA) glycopolymers (GPs). Further, the poly(β-GEMA) chains were grafted onto the silica nanoparticle (SiNP) surface by utilizing the " grafting - from " strategy of surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization to prepare p(β-GEMA)-grafted SiNPs (GNPs). Five different chain lengths ranging from 10 to 40 kDa of the GPs and the GNPs were prepared, and various characterization techniques confirmed the formation of GPs and grafting of the GPs on the SiNP surface. The particle size of GNPs and the number of GPs grafted on the SiNP surface showed a strong dependence on the chain length of the GPs. Further, the GNPs were subjected to a binding study with β-galactose-specific protein peanut agglutinin (PNA). A much stronger binding in the case of GNPs was observed with an association constant ∼320 times and ∼53 times than that of the monomeric methyl-β-d-galactopyranoside and the GPs, respectively. Additionally, the binding of the PNA with GNPs and GPs was also studied with varying chain lengths to understand the effects of the chain length on the binding affinity. A clear increase in binding constants was observed in the case of GNPs with increasing chain length of grafted GPs, attributed to the enhanced enthalpic and entropic contributions. This work holds its uniqueness in these improved interactions between carbohydrates and proteins, which can be used for carbohydrate-based targeted therapeutics.

In this work, we designed biodegradable glycopolymers consisting of a carbohydrate conjugated to a biodegradable polymer, poly(lactic acid) (PLA), through a poly(ethylene glycol) (PEG) linker. The glycopolymers were synthesized by coupling alkyne end-functionalized PEG-PLA with azide-derivatized mannose, trehalose, or maltoheptaose via the click reaction. The coupling yield was in the range of 40–50% and was independent of the size of the carbohydrate. The resulting glycopolymers were able to form micelles with the hydrophobic PLA in the core and the carbohydrates on the surface, as confirmed by binding with the lectin Concanavalin A. The glycomicelles were ~30 nm in diameter with low size dispersity. The glycomicelles were able to encapsulate both non-polar (rifampicin) and polar (ciprofloxacin) antibiotics. Rifampicin-encapsulated micelles were much smaller (27–32 nm) compared to the ciprofloxacin-encapsulated micelles (~417 nm). Moreover, more rifampicin was loaded into the glycomicelles (66–80 μg/mg, 7–8%) than ciprofloxacin (1.2–2.5 μg/mg, 0.1–0.2%). Despite the low loading, the antibiotic-encapsulated glycomicelles were at least as active or 2–4 times more active than the free antibiotics. For glycopolymers without the PEG linker, the antibiotics encapsulated in micelles were 2–6 times worse than the free antibiotics.

[Display omitted] • Glycopolymer-ConA interactions are investigated using turbidity. • The effect of measurement temperature has been found as a significant parameter. • The effect of thermoresponsive repeat units had a significant effect on binding as well. Glycopolymers, a type of synthetic polymer featuring attached carbohydrate components, have emerged as an advanced avenue for different types of biological applications. Their promise stems from their ability to engage in lectin-carbohydrate interactions with specific proteins. In this study, 8 distinct glycopolymers in terms of sugar number, chain length and responsive unit were prepared via Reversible Addition Fragmentation Chain Transfer (RAFT) polymerization. By conducting aggregation, reverse aggregation, and inhibitory potency assays across a temperature range of 10 to 60 ℃, we explored how these parameters influence lectin-carbohydrate interactions in relation to temperature. N,N -dimethylacrylamide (DMA) and N -isopropylacrylamide (NIPAM) were used as a second monomer to synthesize random and block copolymers due to their hydrophilicity and thermal responsive behaviour, respectively. The binding results showed that while all glycopolymers showed faster binding properties at higher temperatures, there was a notable and more significant increase in the case of block co-glycopolymers (P4 and P5) compared to the other glycopolymers. Additionally, the obtained MIC 50 values from inhibitory potency assay proved that all glycopolymers exhibited greater effectiveness as inhibitors of Concanavalin A (Con A) at elevated temperatures. [ABSTRACT FROM AUTHOR]

The emergence and growth of bacterial resistance to antibiotics poses an enormous threat to humanity in the future. In this regard, the discovery of new antibiotics and the improvement of existing ones is a priority task. In this study, we proposed the synthesis of new polymeric conjugates of polymyxin B, which is a clinically approved but limited-use peptide antibiotic. In particular, three carboxylate-bearing polymers and one synthetic glycopolymer were selected for conjugation with polymyxin B (PMX B), namely, poly(α,L-glutamic acid) (PGlu), copolymer of L-glutamic acid and L-phenylalanine (P(Glu-co-Phe)), copolymer of N-vinyl succinamic acid and N-vinylsuccinimide (P(VSAA-co-VSI)), and poly(2-deoxy-2-methacrylamido-D-glucose) (PMAG). Unlike PGlu and PMAG, P(Glu-co-Phe) and P(VSAA-co-VSI) are amphiphilic and form nanoparticles in aqueous media. A number of conjugates with different polymyxin B loading were synthesized and characterized. In addition, the complex conjugates of PGLu or PMAG with polymyxin B and deferoxamine (siderophore) were obtained. A release of PMX B from Schiff base and amide-linked polymer conjugates was studied in model buffer media with pH 7.4 and 5.8. In both cases, a more pronounced release was observed under slightly acidic conditions. The cytotoxicity of free polymers and PMX B as well as their conjugates was examined in human embryonic kidney cells (HEK 293T cell line). All conjugates demonstrated reduced cytotoxicity compared to the free antibiotic. Finally, the antimicrobial efficacy of the conjugates against Pseudomonas aeruginosa was determined and compared. The lowest values of minimum inhibitory concentrations (MIC) were observed for polymyxin B and polymyxin B/deferoxamine conjugated with PMAG. Among the polymers tested, PMAG appears to be the most promising carrier for delivery of PMX B in conjugated form due to the good preservation of the antimicrobial properties of PMX B and the ability of controlled drug release.

Diseases induced by bacterial and viral infections are common occurrences in our daily life, and the main prevention and treatment strategies are vaccination and taking antibacterial/antiviral drugs. However, vaccines can only be used for specific viral infections, and the abuse of antibacterial/antiviral drugs will create multi−drug−resistant bacteria and viruses. Therefore, it is necessary to develop more targeted prevention and treatment methods against bacteria and viruses. Proteins on the surface of bacteria and viruses can specifically bind to sugar, so glycopolymers can be used as potential antibacterial and antiviral drugs. In this review, the research of glycopolymers for bacterial/viral detection/inhibition and antibacterial/antiviral applications in recent years are summarized.

Hybrid nanostructures decorated with glycopolymers are appropriate for biomedical applications. In this paper, the results are obtained from nanographene (NG) decorated with glycoblock copolymer to increase their potential in use in therapies and in examining lectin interactions. A pyren-1-ylmethyl 4-cyano-4-((phenylcarbonothioyl)thio)pentanoate (CPADB-py) chain transfer agent was used in the synthesis of methyl methacrylate glycoblock copolymers (P2 and P3) by reversible addition-fragmentation chain transfer (RAFT) polymerization to adhere the polymer to the nanographene surface. Hybrid nanographenes (NG-1 and NG-2) were obtained by the non-covalent interaction of deprotected P2 and P3 with different fructopyranose groups (3-O-methacryloyl-1,2:4,5-di-O-isopropylidene-ß-D-fructopyranose and 1-O-methacryloyl-2,3:4,5-di-O-isopropylidene-ß-D-fructopyranose) in their backbones. Images obtained from transmission electron microscopy (TEM) of NG-1 and NG-2 show that glycoblock copolymer coating was performed homogeneously. Moreover, thermal gravimetric analysis (TGA) also confirmed a glycoblock copolymer coating of NG-1 and NG-2 by weight loss of 41% and 31%, respectively. In the last step of the study, the binding ability of glycoblock copolymers (P2-hyd and P3-hyd) with concanavalin A (ConA) lectin was investigated by a turbidimetric assay. Promising results were obtained from P3-hyd for the ConA interactions. Hence, this study may open a new avenue in the design of new multifunctional glyconanomaterials that show favorable binding properties with lectins. [ABSTRACT FROM AUTHOR]

Sugar-based polymers have been extensively explored as a means to increase drug delivery systems' biocompatibility and biodegradation. Here,we review he use of sugar-based polymers for drug delivery applications, with a particular focus on the utility of the sugar component(s) to provide benefits for drug targeting and stimuli responsive systems. Specifically, numerous synthetic methods have been developed to reliably modify naturally-occurring polysaccharides, conjugate sugar moieties to synthetic polymer scaffolds to generate glycopolymers, and utilize sugars as a multifunctional building block to develop sugar-linked polymers. The design of sugar-based polymer systems has tremendous implications on both the physiological and biological properties imparted by the saccharide units and are unique from synthetic polymers. These features include the ability of glycopolymers to preferentially target various cell types and tissues through receptor interactions, exhibit bioadhesion for prolonged residence time, and be rapidly recognized and internalized by cancer cells. Also discussed are the distinct stimuli-sensitive properties of saccharide-modified polymers to mediate drug release under desired conditions. Saccharide-based systems with inherent pH- and temperature-sensitive properties, as well as enzyme-cleavable polysaccharides for targeted bioactive delivery, are covered. Overall, this work emphasizes inherent benefits of sugar-containing polymer systems for bioactive delivery.

A class of linear and four-arm mannosylated brush copolymers based on poly(ethylene glycol) and poly(ε-caprolactone) is presented here. The synthesis through ring-opening and atom transfer radical polymerizations provided high control over molecular weight and functionality. A post-polymerization azide–alkyne cycloaddition allowed for the formation of glycopolymers with different mannose valencies (1, 2, 4, and 8). In aqueous media, these macromolecules formed nanoparticles that were able to bind lectins, as investigated by concanavalin A binding assay. The results indicate that carbohydrate–lectin interactions can be tuned by the macromolecular architecture and functionality, hence the importance of these macromolecular properties in the design of targeted anti-pathogenic nanomaterials.

Natural killer (NK) cells, serve as the frontline defense of the immune system, and are capable of surveilling and eliminating tumor cells. Their significance in tumor immunotherapy has garnered considerable attention in recent years. However, the absence of specific receptor-ligand interactions between NK cells and tumor cells hampers their selectivity, thereby limiting the therapeutic effectiveness of NK cell-based tumor immunotherapy. Herein, this work constructs polymannose-engineered NK (pM-NK) cells via metabolic glycoengineering and copper-free click chemistry. Polymannose containing dibenzocyclooctyne terminal groups (pM-DBCO) is synthesized and covalently modified on the surface of azido-labeled NK cells. Compared to the untreated NK cells, the interactions between pM-NK cells and MDA-MB-231 cells, a breast tumor cell line with overexpression of mannose receptors (MRs), are significantly increased, and lead to significantly enhanced killing efficacy. Consequently, intravenous administration of pM-NK cells will effectively inhibit the tumor growth and will prolong the survival of mice bearing MDA-MB-231 tumors. Thus, this work presents a novel strategy for tumor-targeting NK cell-based tumor immunotherapy., (© 2024 Wiley‐VCH GmbH.)

Many viruses exploit the human C-type lectin receptor dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) for cell entry and virus dissemination. An inhibition of DC-SIGN-mediated virus attachment by glycan-derived ligands has, thus, emerged as a promising strategy toward broad-spectrum antiviral therapeutics. In this contribution, several cognate fragments of oligomannose- and complex-type glycans grafted onto a poly-l-lysine scaffold are evaluated as polyvalent DC-SIGN ligands. The range of selected carbohydrate epitopes encompasses linear (α- d-Man-(1→2)-α- d-Man, α- d-Man-(1→2)-α- d-Man-(1→2)-α- d-Man-(1→3)-α- d-Man) and branched (α- d-Man-(1→6)-[α- d-Man-(1→3)]-α- d-Man) oligomannosides, as well as α- l-Fuc. The thermodynamics of binding are investigated on a mono- and multivalent level to shed light on the molecular details of the interactions with the tetravalent receptor. Cellular models of virus attachment and DC-SIGN-mediated virus dissemination reveal a high potency of the presented glycopolymers in the low pico- and nanomolar ranges, respectively. The high activity of oligomannose epitopes in combination with the biocompatible properties of the poly- l-lysine scaffold highlights the potential for further preclinical development of polyvalent DC-SIGN ligands., (© 2023 The Authors. Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

Inverse vaccines that tolerogenically target antigens to antigen-presenting cells (APCs) offer promise in prevention of immunity to allergens and protein drugs and treatment of autoimmunity. We have previously shown that targeting hepatic APCs through intravenous injection of synthetically glycosylated antigen leads to effective induction of antigen-specific immunological tolerance. Here, we demonstrate that targeting these glycoconjugates to lymph node (LN) APCs under homeostatic conditions leads to local and increased accumulation in the LNs compared to unmodified antigen and induces a tolerogenic state both locally and systemically. Subcutaneous administration directs the polymeric glycoconjugate to the draining LN, where the glycoconjugated antigen generates robust antigen-specific CD4+ and CD8+ T cell tolerance and hypo-responsiveness to antigenic challenge via a number of mechanisms, including clonal deletion, anergy of activated T cells, and expansion of regulatory T cells. Lag-3 up-regulation on CD4+ and CD8+ T cells represents an essential mechanism of suppression. Additionally, presentation of antigen released from the glycoconjugate to naïve T cells is mediated mainly by LN-resident CD8+ and CD11b+ dendritic cells. Thus, here we demonstrate that antigen targeting via synthetic glycosylation to impart affinity for APC scavenger receptors generates tolerance when LN dendritic cells are the cellular target. [ABSTRACT FROM AUTHOR]

Inverse vaccines that tolerogenically target antigens to antigen-presenting cells (APCs) offer promise in prevention of immunity to allergens and protein drugs and treatment of autoimmunity. We have previously shown that targeting hepatic APCs through intravenous injection of synthetically glycosylated antigen leads to effective induction of antigen-specific immunological tolerance. Here, we demonstrate that targeting these glycoconjugates to lymph node (LN) APCs under homeostatic conditions leads to local and increased accumulation in the LNs compared to unmodified antigen and induces a tolerogenic state both locally and systemically. Subcutaneous administration directs the polymeric glycoconjugate to the draining LN, where the glycoconjugated antigen generates robust antigen-specific CD4+ and CD8+ T cell tolerance and hypo-responsiveness to antigenic challenge via a number of mechanisms, including clonal deletion, anergy of activated T cells, and expansion of regulatory T cells. Lag-3 up-regulation on CD4+ and CD8+ T cells represents an essential mechanism of suppression. Additionally, presentation of antigen released from the glycoconjugate to naïve T cells is mediated mainly by LN-resident CD8+ and CD11b+ dendritic cells. Thus, here we demonstrate that antigen targeting via synthetic glycosylation to impart affinity for APC scavenger receptors generates tolerance when LN dendritic cells are the cellular target.

Glycosyl monomers for the assembly of multivalent ligands are typically synthesized using carbohydrates with biological functions and polymerizable functional groups such as acrylamide or styrene introduced into the carbohydrate aglycon, and monomers polymerized using a radical initiator. Herein, we report the acryloylation of 6-aminohexyl α-d-mannoside and its conversion into the glycosyl monomer bearing an acrylamide group. The general acryloylation procedure afforded the desired N-hexyl α-d-acetylmannosyl acrylamide monomer as well as an unexpected compound with a close Rf value. The compounds were separated and analyzed by nuclear magnetic resonance spectroscopy and mass spectrometry, which revealed the unknown compound to be the bivalent N,N-bis(hexyl α-d-acetylmannosyl) acrylamide monomer, which contains two hexyl mannose units and one acrylamide group. To the best of our knowledge, this side reaction has not previously been disclosed, and may be useful for the construction of multivalent sugar ligands.

Methacryl-2,3,4,6-tetra-O-acetyl-D-galactopyranoside (MG) based linear (PMG-L), 3-armed (PMG-3A) and 4-armed (PMG-4A) galactopolymer architectures were produced by ATRP copper complexed process and the obtained polymer architectures were characterized by FT-IR and 1H- & 13C-NMR spectroscopic techniques. The weight percentages of pendant protected galactose moieties of the galactomacromolecular chains were in the range of 74.3-77.9 % and the molecular weights of the galactopolymers were in the orbit of 10595-13211 as calculated from 1H-NMR spectra. Further, graphene oxide (GO) was functionalized with 2-thiopheneethylamine (GO-T) and RGD peptide (GO-P) and their nanocomposites were prepared with the synthesized PMG-L, PMG-3A, and PMG-4A galactopolymers by solvent assisted–mixing method. The 4-armed nanocomposites exhibited 5-12 °C higher thermal stability compared to the neat galactopolymers. DSC studies of the neat galactopolymers and nanocomposites revealed that the PMG-3A nanocomposites with 1 wt% GO and modified GO showed higher glass transition temperature values (98-129 °C) compared to their neat galactopolymer (92 °C). FE-SEM analysis of nanocomposites revealed the dependence of polymer architecture and GO surface functionalities on the surface morphologies. The 4-armed polymer composites having 1 wt% of GO-P and GO-T showed the formation of relatively uniform spherical 150-200 nm nanoparticles. Antibacterial activities of the PMG-L, PMG-3A, and PMG-4A nanocomposites were evaluated against E. coli and compared with their neat galactopolymer architectures. The PMG-3A and PMG-4A galactopolymer nanocomposites exhibited considerably prominent zone of inhibition in contrast to the linear polymer, PMG-L nanocomposites and their neat galactopolymers. [ABSTRACT FROM AUTHOR]

Carbohydrates play essential structural and biochemical roles in all living organisms. Glycopolymers are attractive as well-defined biomimetic analogs to study carbohydrate-dependent processes, and are widely applicable biocompatible materials in their own right. Glycopolypeptides have shown great promise in this area since they are closer structural mimics of natural glycoproteins than other synthetic glycopolymers and can serve as carriers for biologically active carbohydrates. This review highlights advances in the area of design and synthesis of such materials, and their biomedical applications in therapeutic delivery, tissue engineering, and beyond. Unlabelled Image [ABSTRACT FROM AUTHOR]

Glycopolymer-grafted gold nanorods (GlycoAuNRs) were designed and fabricated as a heptoma-targeting phototherapy nanoparticles. The block glycopolymer, poly (diethyleneglycol methacrylate)-block-poly(6-O-vinyladipoyl-α-D-galactose) (PDEGMA-b-POVNGA), was synthesized by RAFT polymerization and modified AuNRs with Au-S bonds via reducing the thioester at the end of glycopolymer to thiol (–SH). Galactose pendants of thermosensitive AuNRs@PDEGMA-b-POVNGA were exposed when the temperature of aqueous dispersion is above lower critical solution temperature, which was responsible for specific binding ability with ricinus communis agglutinin. In vitro experiment indicated that the synthesized glycopolymer could significantly improve cytocompatibility of AuNRs and target to hepatocellular carcinoma cells, owing to the galactose moiety that recognized the overexpressed asialoglycoprotein receptor on the hepatocellular carcinoma cells. Interestingly, the addition of ricinus communis agglutinin could inhibit the growth of the hepatocellular carcinoma cells in some extent. Furthermore, the photothermal therapy assay proved that glycoAuNRs-ricinus communis agglutinin could realize highly effective photothermal treatment for the tumor cells in vitro upon laser irradiation by cooperative effect. [ABSTRACT FROM AUTHOR]

Glycosaminoglycans (GAGs) are naturally existing extracellular components with a variety important biological functions. However, their heterogeneous chemical compositions and the challenges in purification have become the main disadvantages for clinical applications. Thus, various synthetic glycopolymers have been designed to mimic the structures and functions of natural GAGs. In the current study, glycopolymers from structurally simple glucose or N -acetylglucosamine monomers were synthesized, which were further subjected to sulfation of different degrees and grafting onto silica nanoparticles, leading to spherical-shaped nano-structures of uniform diameters. With the successively strengthened multivalent effect, the obtained glycopolymer nanoparticles not only showed excellent effects on promotion of cell proliferation by stabilizing growth factors, but also significantly inhibited tumor metastasis by weakening the adhesion between tumor cells and activated platelets. Among the prepared nanoparticles, S 3 -PGNAc@Si with N -acetylglucosamine segment and the highest sulfation degree exhibited the strongest bioactivities, which were even close to those of heparin. This work presents a novel approach for structural and functional mimicking of natural GAGs from simple and low-cost monosaccharides, holding great potential for a range of biomedical applications. [ABSTRACT FROM AUTHOR]

[Display omitted] • Star glycopolymer with aggregation-induced emission effect was synthesized by reversible deactivation radical polymerization. • The glycopolymer could act as fluorescent probe to detect boric acid in the range of 10–8000 mg/mL. Excessive boric acid could cause severe damage to plants and humans. Hence, it is of great importance to detect its presence in water. However, traditional analytical methods often have to use either toxic reagents or expensive instruments, which urges the development of a facile detection strategy. Herein, we have designed a tetraphenylethylene-cored glucose-containing glycopolymer with an aggregation-induced emission effect to detect the concentration of boric acid in water efficiently. Copper-mediated reversible deactivation radical polymerization (Cu(0)-RDRP) was utilized to polymerize glucose-containing monomer directly in N, N -dimethylbenzamide (DMF), yielding a star-shaped glycopolymer with a tetraphenylethylene core. This glycopolymer emitted fluorescence through B(OH) 4 − induced aggregation under alkaline conditions, which can serve as a sensitive fluorescence probe for detecting boric acid while being specific to the acid and not affected by other metal ions. [ABSTRACT FROM AUTHOR]

Shaofeng Lou,1 Xiuyuan Zhang,2 Mingming Zhang,2 Shenglu Ji,1 Weiwei Wang,2 Ju Zhang,1 Chen Li,2 Deling Kong1,2 1Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, 2Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin, People’s Republic of China Abstract: A reductase-cleavable and thermo-responsive star-shaped polymer nanogel was prepared via an “arm-first” atom transfer radical polymerization approach. The nanogel consists of a thermo- and redox-sensitive core and a zwitterionic copolymer block. The dual sensitive core is composed of poly(N-isopropylacrylamide) that is formed by disulfide crosslinking of N-isopropylacrylamide. The zwitterionic copolymer block contains a poly(sulfobetaine methacrylate) component, a known anti-adsorptive moiety that extends blood circulation time, and a lactose motif of poly(2-lactobionamidoethyl methacrylamide) that specifically targets the asialoglycoprotein receptors (ASGP-Rs) of hepatoma. Doxorubicin (DOX) was encapsulated into the cross-linked nanogels via solvent extraction/evaporation method and dialysis; average diameter of both blank and DOX-loaded nanogels was ~120 nm. The multi-responsiveness of nanogel drug release in different temperatures and redox conditions was assessed. After 24 h, DOX release was only ~20% at 30°C with 0 mM glutathione (GSH), whereas over 90% DOX release was observed at 40°C and 10 mM GSH, evidence of dual responsiveness to temperature and reductase GSH. The IC50 value of DOX-loaded nanogels was much lower in human hepatoma (HepG2) cells compared to non-hepatic HeLa cells. Remarkably, DOX uptake of HepG2 cells differed substantially in the presence and absence of galactose (0.31 vs 1.42 µg/mL after 48 h of incubation). The difference was non-detectable in HeLa cells (1.21 vs 1.57 µg/mL after 48 h of incubation), indicating that the overexpression of ASGP-Rs leads to the DOX-loaded lactosylated nanogels actively targeting hepatoma. Our data indicate that the lactose-decorated star-shaped nanogels are dual responsive and hepatoma targeted, and could be employed as hepatoma-specific anti-cancer drug delivery vehicle for cancer chemotherapy. Keywords: glycopolymer, multi-responsive nanogel, hepatoma targeting, drug delivery, arm-first ATRP