Metal-Free Atom Transfer Radical Polymerization to Prepare Recylable Micro-Adjuvants for Dendritic Cell Vaccine.

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.

Well-Defined Oligo(azobenzene-graft-mannose): Photostimuli Supramolecular Self-Assembly and Immune Effect Regulation.

The immune system can recognize and respond to pathogens of various shapes. Synthetic materials that can change their shape have the potential to be used in vaccines and immune regulation. The ability of supramolecular assemblies to undergo reversible transformations in response to environmental stimuli allows for dynamic changes in their shapes and functionalities. A meticulously designed oligo(azobenzene-graft-mannose) was synthesized using a stepwise iterative method and "click" chemistry. This involved integrating hydrophobic and photoresponsive azobenzene units with hydrophilic and bioactive mannose units. The resulting oligomer, with its precise structure, displayed versatile assembly morphologies and chiralities that were responsive to light. These varying assembly morphologies demonstrated distinct capabilities in terms of inhibiting the proliferation of cancer cells and stimulating the maturation of dendritic cells. These discoveries contribute to the theoretical comprehension and advancement of photoswitchable bioactive materials.

Multifunctional, Degradable Wearable Sensors Prepared with an Initiator and Crosslinker-Free Method.

The present zwitterionic hydrogel-based wearable sensor exhibits various limitations, such as limited degradation capacity, unavoidable toxicity resulting from initiators, and poor mechanical properties that cannot satisfy practical demands. Herein, we present an initiator and crosslinker-free approach to prepare polyethylene glycol (PEG)@poly[2-(methacryloyloxy)ethyl] dimethyl-(3-sulfopropyl) (PSBMA) interpenetrating polymer network (IPN) hydrogels that are self-polymerized via sunlight-induced and non-covalent crosslinking through electrostatic interaction and hydrogen bonding among polymer chains. The PEG@PSBMA IPN hydrogel possesses tissue-like softness, superior stretchability (∼2344.6% elongation), enhanced fracture strength (∼39.5 kPa), excellent biocompatibility, antibacterial property, reliable adhesion, and ionic conductivity. Furthermore, the sensor based on the IPN hydrogel demonstrates good sensitivity and cyclic stability, enabling effective real-time monitoring of human body activities. Moreover, it is worth noting that the excellent degradability in the saline solution within 8 h makes the prepared hydrogel-based wearable sensor free from the electronic device contamination. We believe that the proposed strategy for preparing physical zwitterionic hydrogels will pave the way for fabricating eco-friendly wearable devices.

Impact of Graphitization Degree on the Electrochemical and Thermal Properties of Coal.

Coal-based cryptocrystalline graphite is an intermediate phase formed during the transformation of highly metamorphic anthracite into crystalline graphite. In order to explore the relationship between the graphitization degree of coal-based cryptocrystalline graphite and its physical properties from macromolecular structure to provide a theoretical basis for industrial application, samples were tested by X-ray diffraction, electrochemistry, and thermal conductivity and compared with standard graphite (SG) and artificial thermal simulation graphitized samples. The results show that with the increase of graphitization degree and the growth of microcrystalline structure, the electrical impedance of cryptocrystalline graphite decreases, the conductivity increases, the specific capacity of initial discharge increases, and the thermal conductivity increases, which gradually approach the electrical and thermal properties of crystalline graphite. The linear equations between impedance and La and Lc are y = -0.42x + 70.44 and y = -1.87x + 70.62, and the correlation coefficients are 0.93 and 0.88. The linear equations between thermal conductivity and the horizontal extension length (La) and vertical stacking thickness (Lc) are y = 0.09x + 1.36 and y = 0.4x + 0.76, the correlation coefficients are 0.82 and 0.84., and the reduction of microcrystalline parameters d002 and the increase of La and Lc lead to a direct improvement of physical properties. Artificial thermal simulation samples also show the same regularity, but their physical properties are lower than those of natural evolution samples. Short-term high-temperature simulation is different from long-term magma heat and pressure, and the growth of graphite microcrystals is more complete under long-term geological conditions, resulting in better physical properties.

Microstructure-dependent CO2-responsive microemulsions for deep-cleaning of oil-contaminated soils.

CO2-responsive microemulsion (ME) is considered a promising candidate for deep-cleaning and oil recovery from oil-contaminated soils. Understanding the responsive nature of different microstructures (i.e., oil-in-water (O/W), bicontinuous (B.C.) and water-in-oil (W/O)) is essential for unlocking the potential and mechanisms of CO2-responsive emulsions in complex multiphase systems and providing comprehensive guidance for remediation of oil-contaminated soils. Herein, the responsiveness of microstructures of ME to CO2 trigger was investigated using experimental designs and coarse-grained molecular dynamic simulations. MEs were formed for the first time by a weakly associated pseudo-Gemini surfactant of indigenous organic acids (naphthenic acids, NAs are a class of natural surface-active molecules in crude oil) and tetraethylenepentamine (TEPA) through fine tuning of co-solvent of dodecyl benzene sulfonic acid (DBSA) and butanol. The O/W ME exhibited an optimal CO2-responsive character due to easier proton migration in the continuous aqueous phase and more pronounced dependence of configuration on deprotonated NA ions. Conversely, the ME with W/O microstructure exhibited a weak to none responsive characteristic, most likely attributed to its high viscosity and strong oil-NA interactions. The O/W ME also showed superior cleaning efficiency and oil recovery from oil-contaminated soils. The results from this study provide insights for the design of CO2-responsive MEs with desired performance and guidance for choosing the favorable operating conditions in various industrial applications, such as oily solid waste treatment, enhanced oil recovery (EOR), and pipeline transportation. The insights from this work allow more efficient and tailored design of switchable MEs for manufacturing advanced responsive materials in various industrial sectors and formulation of household products.

Differences in Molecular Structure between Vitrinite and Inertinite and Their Impact on Coal Conversion and Utilization.

To compare the differences in chemical structure between vitrinite and inertinite and their effects on transformation and utilization, this paper separated vitrinite and inertinite from three parent coal samples (high-volatile bituminous coal (Rmax (%) = 0.65), medium-volatile bituminous coal (Rmax (%) = 1.25), and low-volatile bituminous coal (Rmax (%) = 1.7)), and the differences in chemical structure were analyzed from three aspects: aromatic structure, aliphatic structure, and cross-linking structure. The molecular structure model of a single maceral was constructed, and the chemical bond parameters and the impact on coal conversion and utilization were analyzed. The results showed that (i) in the same sample, inertinite has advanced evolution characteristics, higher aromaticity, and ring condensation degree, but vitrinite has a faster evolution rate than inertinite. (ii) The molecular structure model shows that with the increase of the evolution degree of samples, the proportion of polycyclic aromatic hydrocarbons increased gradually. After molecular dynamics simulations, the cross-linked structures in the planar macromolecular structure have huge torsion deformation, and the torsion of aromatic structure decreased from benzene, naphthalene, anthracene, and phenanthrene. (iii) The analysis of chemical bond parameters showed that the ether-oxygen bond with shorter bond length and higher bond energy is a key factor hindering the breakage recombination of the macromolecular structure. In the high-evolution stage, the ether carbon content in inertinite is higher than that in vitrinite and has a stronger cross-linking structure. Therefore, it is less reactive in the transformation processes of coking and gasification. However, inertinite has larger aromatic layers and a more ordered orientation, which has certain advantages in the preparation of coal-based graphite.

Advancing cell surface modification in mammalian cells with synthetic molecules.

Biological cells, being the fundamental entities of life, are widely acknowledged as intricate living machines. The manipulation of cell surfaces has emerged as a progressively significant domain of investigation and advancement in recent times. Particularly, the alteration of cell surfaces using meticulously crafted and thoroughly characterized synthesized molecules has proven to be an efficacious means of introducing innovative functionalities or manipulating cells. Within this realm, a diverse array of elegant and robust strategies have been recently devised, including the bioorthogonal strategy, which enables selective modification. This review offers a comprehensive survey of recent advancements in the modification of mammalian cell surfaces through the use of synthetic molecules. It explores a range of strategies, encompassing chemical covalent modifications, physical alterations, and bioorthogonal approaches. The review concludes by addressing the present challenges and potential future opportunities in this rapidly expanding field.

Glycopolymers With On/Off Anchors: Confinement Effect on Regulating Dendritic Cells.

Insufficient activation or over-activation of T cells due to the dendritic cells (DCs) state can cause negative effects on immunotherapy, making it crucial for DCs to maintain different states in different treatments. Polysaccharides are one of the most studied substances to promote DCs maturation. However, in many methods, optimizing the spatial dimension of the interaction between polysaccharides and cells is often overlooked. Therefore, in this study, a new strategy from the perspective of spatial dimension is proposed to regulate the efficacy of polysaccharides in promoting DCs maturation. An anchoring molecule (DMA) is introduced to existing glycopolymers for the confinement effect, and the effect can be turned off by oxidation of DMA. Among the prepared on-confined (PMD2 ), off-confined (PMD2 -O), and norm (PM2 ) glycopolymers, PMD2 and PMD2 -O show the best and worst results, respectively, in terms of the amount of binding to DCs and the effect on promoting DCs maturation. This sufficiently shows that the turn-on and off of confinement effect can regulate the maturation of DCs by polysaccharides. Based on the all-atom molecular dynamics (MD) simulation, the mechanism of difference in the confinement effect is explained. This simple method can also be used to regulate other molecule-cell interactions to guide cell behavior.

Glycopolymers for Antibacterial and Antiviral Applications.

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.

Surface-Initiated Synthesis of Cell-Specific Glycopolymers Using Live Mammalian Cells as Templates.

Molecular recognition is an important process in life activities where specificity is the key. However, the method to gain specificity are often complex and time-consuming. Herein, a novel, versatile, and effective way is developed to obtain cell-specific glycosurfaces by surface-initiated Cu-mediated reversible deactivation radical polymerization (Cu-RDRP) in an open to air fashion. Mammalian cells are used for the first time as live templates to realize cell-sugar monomer-aptation-polymerization which can produce cell-specific glycosurfaces. Both epithelial cell adhesion molecule (EpCAM) positive cells L929 and EpCAM negative cells Hela as models are used to acquire two cell-specific glycosurfaces, which can distinguish template-cells from others. The strategy is effective and convenient without the need of fixative pretreatment of cells. It is found that the specific capture does not rely on EpCAM antibodies, and the specificity is related to the composition and chain sequence of the glycopolymer brushes rather than surface morphology. In addition, these glycosurfaces keep the ability to identify the target cells after ten regenerative treatments, which provides another advantage for practical applications.

Switchable RAFT Polymerization Employing Photoresponsive HABI as a Mediator.

Recently, considerable interest has been devoted to developing switchable reversible addition fragmentation chain transfer (RAFT) polymerizations via photoactivation methods. Herein, a photo-deactivation strategy is introduced to regulate RAFT polymerization using photoresponsive hexaarylbiimidozole (HABI) as a mediator, which leads to switchable RAFT polymerization by repeated ON/OFF experiments. In comparison with well-known PET-RAFT polymerization, photo-deactivation RAFT (PD-RAFT) polymerization can be temporally stopped with UV light ON, where photoresponsive HABI can reversibly quench propagating radicals, resulting in switchable RAFT polymerization. The proposed mechanism of PD-RAFT polymerization in the presence of HABI involving radical quenching is based on ESR, NMR, GPC, MALDI-TOF-MS, and kinetics studies.

Degradable Selenium-Containing Polymers for Low Cytotoxic Antibacterial Materials.

Developing biodegradable cationic polymers with high antibacterial efficiency and low cytotoxicity is of great significance in biological applications. Selenium is an essential trace element for the human body, and selenium-containing compounds are promising in various health-related applications. To combine selenium with biodegradability, selenide-functionalized polycaprolactones (PCL) with different hydrophobic substituents were synthesized followed by selenoniumization. The optimal polyselenonium salt showed excellent antibacterial activity with an MBC of 2 µg mL-1 and an MIC of 1 µg mL-1 and exhibited good biocompatibility before and after degradation. In addition, the obtained selenium polymer can be well blended with commercial PCL by electrospinning, and films with good antibacterial activity were prepared. This work enriches the knowledge of selenium derivatives and lays a foundation for follow-up research on selenium cationic polymers in the antimicrobial field.

In situ preparation of glyco-micromotors and their bacteria loading/guiding ability.

We successfully synthesized glyco-micromotors in situ directed by multifunctional glycopolymers, which were obtained by copolymerizing 2-methacrylamido glucopyranose (MAG) and 2-(diethylamino)ethyl methacrylate (DEAEMA) monomers. The fabricated glyco-micromotors present abilities in loading and guiding bacteria with different individual and group motions.

Towards a protein-selective Raman enhancement by a glycopolymer-based composite surface.

Surface-enhanced Raman scattering (SERS), which is based on the surface plasmon resonance (LSPR) of noble metal nanostructures, is widely used in the biological field due to its advantages of non-damaging samples and detection up to the molecular level. For biological SERS detection, preparation of substrates with biocompatibility and specific adsorption, leading to selective enhancement of the target biomolecules, are important design strategies. Utilizing the specific interaction between a carbohydrate and protein, a glycopolymer-based composite surface is fabricated to realize specific SERS detection of proteins. Herein, we use N-3,4-dihydroxybenzeneethyl methacrylamide (DMA), 2-deoxy-2-(methacrylamido)glucopyranose (MAG) and methacrylic acid (MAA) as monomers in a sunlight-induced RAFT polymerization to synthesize a dopamine-containing glycopolymer. The glycopolymers are used to prepare a SERS substrate. The composite surface shows specific protein adsorption capacity, and the selective Raman enhancement of specific proteins was successfully achieved between the two different proteins Con A and BSA. This provides a feasible approach to design a SERS surface for protein detection and the study of the interaction between sugar and proteins.

Glycopolymer Engineering of the Cell Surface Changes the Single Cell Migratory Direction and Inhibits the Collective Migration of Cancer Cells.

Cancer cell migration is one of the most important processes in cancer metastasis. Metastasis is the major cause of death from most solid tumors; therefore, suppressing cancer cell migration is an important means of reducing cancer mortality. Cell surface engineering can alter the interactions between cells and their microenvironment, thereby offering an effective method of controlling the migration of the cells. This paper reports that modification of the mouse melanoma (B16) cancer cell surface with glycopolymers affects the migration of the cells. Changes in cell morphology, migratory trajectories, and velocity were investigated by time-lapse cell tracking. The data showed that the migration direction is altered and diffusion slows down for modified B16 cells compared to unmodified B16 cells. When modified and unmodified B16 cells were mixed, wound-healing experiments and particle image velocimetry (PIV) analysis showed that the collective migration of unmodified B16 cells was suppressed because of vortexlike motions induced by the modified cells. The work demonstrates the important role of surface properties/modification in cancer cell migration, thereby providing new insights relative to the treatment of cancer metastasis.

Synthetic Sugar-Only Polymers with Double-Shoulder Task: Bioactivity and Imaging.

The search for novel fluorescent materials has attracted the attention of many researchers. Numerous bioimaging materials based on the aggregation-induced emission (AIE) units have been surging and could be employed in wide areas during the past two decades. In recent few years, the appearance of nonconventional fluorescence emitters without aromatic conjugated structures provides another bioimaging candidate which has the advantage of enhanced biodegradability and relatively low cost, and their luminescent mechanism can be explained by clustering-triggered emission (CTE) like AIE. In our contribution, we utilize nonaromatic sugar as a monomer to prepare a series of glycopolymers with designed components through sunlight-induced reversible addition fragmentation chain transfer polymerization; these glycopolymers can be employed in bioimaging fields due to the bioactivity coming from sugar and CTE capacity.

Encapsulation of Photothermal Nanoparticles in Stealth and pH-Responsive Micelles for Eradication of Infectious Biofilms In Vitro and In Vivo.

Photothermal nanoparticles can be used for non-antibiotic-based eradication of infectious biofilms, but this may cause collateral damage to tissue surrounding an infection site. In order to prevent collateral tissue damage, we encapsulated photothermal polydopamine-nanoparticles (PDA-NPs) in mixed shell polymeric micelles, composed of stealth polyethylene glycol (PEG) and pH-sensitive poly(ß-amino ester) (PAE). To achieve encapsulation, PDA-NPs were made hydrophobic by electrostatic binding of indocyanine green (ICG). Coupling of ICG enhanced the photothermal conversion efficacy of PDA-NPs from 33% to 47%. Photothermal conversion was not affected by micellar encapsulation. No cytotoxicity or hemolytic effects of PEG-PAE encapsulated PDA-ICG-NPs were observed. PEG-PAE encapsulated PDA-ICG-NPs showed good penetration and accumulation in a Staphylococcus aureus biofilm. Penetration and accumulation were absent when nanoparticles were encapsulated in PEG-micelles without a pH-responsive moiety. PDA-ICG-NPs encapsulated in PEG-PAE-micelles found their way through the blood circulation to a sub-cutaneous infection site after tail-vein injection in mice, yielding faster eradication of infections upon near-infrared (NIR) irradiation than could be achieved after encapsulation in PEG-micelles. Moreover, staphylococcal counts in surrounding tissue were reduced facilitating faster wound healing. Thus, the combined effect of targeting and localized NIR irradiation prevented collateral tissue damage while eradicating an infectious biofilm.

Immune Effect Regulated by the Chain Length: Interaction between Immune Cell Surface Receptors and Synthetic Glycopolymers.

Glycopolymer-based drugs for immunotherapy have attracted increasing attention because the affinity between glycans and proteins plays an important role in immune responses. Previous studies indicate that the polymer chain length influences the affinity. In the studies on enhancing the immune response by glycans, it is found that both oligosaccharides and long-chain glycopolymers work well. However, there is a lack of systematic studies on the immune enhancement effect and the binding ability of oligomers and polymers to immune-related proteins. In this paper, to study the influence of the chain length, glycopolymers based on N-acetylglucosamine with different chain lengths were synthesized, and their interaction with immune-related proteins and their effect on dendritic cell maturation were evaluated. It was proved that compared with l-glycopolymers (degree of polymerization (DP) > 20), s-glycopolymers (DP < 20) showed better binding ability to the dendritic cell-specific ICAM-3-grabbing nonintegrin protein and the toll-like receptor 4 and myeloid differentiation factor 2 complex protein by quartz crystal microbalance and molecular docking simulation. When the total sugar unit amounts are equal, s-glycopolymers are proved to be superior in promoting dendritic cell maturation by detecting the expression level of CD80 and CD86 on the surface of dendritic cells. Through the combination of experimental characterization and theoretical simulation, a deep look into the interaction between immune-related proteins and glycopolymers with different chain lengths is helpful to improve the understanding of the immune-related interactions and provides a good theoretical basis for the design of new glycopolymer-based immune drugs.

Polymerization in Shear Flow: From Bowl-Shaped Glyco-Microcarriers to Self-Propelled Micromotors.

We report a simple and effective method to synthesize composite bowl-shaped colloidal particles composed of a magnetic bottom and polymer wall. The bowl-shape is determined by the stirring and the resulting centrifugal force acting on the components during the synthesis. By systematically varying the stirring speed, we have found the lower and upper bounds for the bowl formation. Moreover, the size and thickness of the bowl can be tuned by changing the amount of the TPM monomer during synthesis. Functional groups can be easily introduced in the solidifying step through the polymerization of TPM by adding initiators and functional monomers. For example, by copolymerization of glycomonomer with TPM, bowl-shaped particles with biological activity can be obtained. In addition, such composite particles can be further modified to produce micromotors with well-controlled motions.

Thermo-resistance of ESKAPE-panel pathogens, eradication and growth prevention of an infectious biofilm by photothermal, polydopamine-nanoparticles in vitro.

Nanotechnology offers many novel infection-control strategies that may help prevent and treat antimicrobial-resistant bacterial infections. Here, we synthesized polydopamine, photothermal-nanoparticles (PDA-NPs) without further surface-functionalization to evaluate their potential with respect to biofilm-control. Most ESKAPE-panel pathogens in suspension with photothermal-nanoparticles showed three- to four-log-unit reductions upon Near-Infra-Red (NIR)-irradiation, but for enterococci only less than two-log unit reduction was observed. Exposure of existing Staphylococcus aureus biofilms to photothermal-nanoparticles followed by NIR-irradiation did not significantly kill biofilm-inhabitants. This indicates that the biofilm mode of growth poses a barrier to penetration of photothermal-nanoparticles, yielding dissipation of heat to the biofilm-surrounding rather than in its interior. Staphylococcal biofilm-growth in the presence of photothermal-nanoparticles could be significantly prevented after NIR-irradiation because PDA-NPs were incorporated in the biofilm and heat dissipated inside it. Thus, unmodified photothermal nanoparticles have potential for prophylactic infection-control, but data also constitute a warning for possible development of thermo-resistance in infectious pathogens.