Zwitterionic Surface Research Articles

Ice Adhesion to Cationic, Anionic, Zwitterionic, and Nonionic Polymer Surfaces

Ice Adhesion to Cationic, Anionic, Zwitterionic, and Nonionic Polymer Surfaces

Light-responsive zwitterionic membrane surface modification for antifouling and antibacterial application

Light-responsive surface modifications offer a promising solution for reducing membrane fouling by enabling remote, contactless cleaning without altering the chemical environment. While traditional methods make membranes hydrophilic to resist fouling, biofouling remains difficult to remove and often requires harsh bactericidal treatments. With the rise of antimicrobial resistance (AMR), there is a pressing need for alternative, non-bactericidal strategies to control biofilm growth. In this study, we developed an efficient approach by coating commercial ultrafiltration polyethersulfone (PES) membranes with a copolymer of light-responsive azobenzene (AZO) and zwitterionic sulphobetaine methacrylate (SBMA). The photochemical conversion efficiency and photokinetic parameters of the copolymer, due to light-induced trans–cis-trans conversion, were systematically determined. During filtration, the modified membranes showed excellent resistance to reversible fouling with bovine serum albumin (BSA). The fouled membrane became reusable after near-complete removal of irreversible fouling, including bacteria (Pseudomonas aeruginosa), by activating the AZO units with UV–vis light, providing an effective strategy for fouling control.

Photobleaching-mediated charge-convertible cyclodextrin nanoparticles achieve deep tumour penetration for rectal cancer theranostics.

Although charge-converting nanoparticles (NPs) potentially penetrate tumours deeply, conventional charge conversion strategies possess limitations, including low selectivity and slow, inconsistent conversion rate within the tumour microenvironment. In this study, we synthesized a zwitterionic near-infrared cyclodextrin derivative of heptamethine cyanine and complexed it with pheophorbide-conjugated ferrocene to produce multifunctional theranostic nanotherapeutics. Our NPs demonstrated enhanced tumour-targeting ability, enabling the highly specific imaging of rectal tumours, with tumour-to-rectum signal ratios reaching up to 7.8. The zwitterionic surface charge of the NPs was rapidly converted to a cationic charge within the tumours on 880 nm near-infrared laser irradiation, promoting the tumoural penetration of NPs via transcytosis. After penetration, photodynamic/chemodynamic therapy was initiated using a 660 nm laser. Our NPs eradicated clinically relevant-sized heterotopic tumours (~250 mm3) and orthotopic rectal tumours, displaying their potential as theranostic nanoplatforms for targeting rectal cancer.

Construction of zwitterionic surface of PVDF hollow fiber membrane and the study on the mechanism of “autonomy-response” synergistic enhancement anti-fouling

In this study, polyvinylidene fluoride (PVDF)/styryl maleic anhydride (SMA) hollow fiber membrane was fabricated using the Thermally Induced Phase Separation (TIPS) technique. Subsequently, zwitterion-sulfobetaine methacrylate (SBMA) was introduced to the membrane surface through a Michael addition reaction to create a nearly electrically neutral membrane surface. This modification effectively mitigated the high adsorption of differently charged protein pollutants on the membrane surface, thereby enhancing its anti-fouling performance. Simultaneously, the membrane surfaces with positive and negative charges were separately constructed, and the impact of membrane surface charge properties on the anti-fouling performance against positively and negatively charged foulants was investigated. Furthermore, detailed studies were conducted on the chemical structure, surface morphology, performance, and anti-fouling mechanism of the modified membranes. The results indicate that the electrically neutral membrane modified by zwitterionic SBMA exhibited excellent anti-fouling properties against both bovine serum albumin (BSA) and lysozyme (LYZ), with a flux recovery rate (FRR) reaching 96.5 % and 94.6 %, respectively. The static adsorption capacities of BSA and LYZ on the membrane surface decreased to 5.89 μg cm−2 and 9.53 μg cm−2, respectively. Furthermore, the study investigated the structure of the hydration layer formed by zwitterionic SBMA on the membrane surface, as well as its hydration capacity and anti-fouling mechanism. Subsequently, through an assessment of the long-term stability of the modified membrane and its flux recovery rate (FRR), in conjunction with theories related to hydration layers and thermodynamics, it elucidated the anti-fouling mechanism involving “autonomy-response” synergistic enhancement of zwitterions. These findings will offer new strategies for researching hollow fiber membranes with superior anti-fouling properties and for applying zwitterions in membrane technology.

Salt-Screened Transition toward Bulk-Like Water Dynamics near Polymeric Zwitterions.

The superior antifouling performance of zwitterionic materials is commonly linked to their hydration structure, in which tight surface binding of water molecules inhibits solute adsorption. However, there is comparatively little direct experimental data on the hydration water structure and dynamics around zwitterionic moieties, including the longer-range behavior of the hydration shell that modulates the approach of solutes to the polymer surface. This work experimentally probes the dynamics of the diffusing hydration water molecules around a series of zwitterion chemistries using Overhauser dynamic nuclear polarization relaxometry. Surprisingly, water dynamics measured within ∼1 nm of the zwitterions were minimally inhibited compared to those near uncharged hydrophilic or cationic side chains. Specific dissolved ions further enhance the water diffusivity near the zwitterions, rendering the hydration shell bulk water-like. These results that the hydration of a zwitterion surface is nearly indistinguishable from bulk water suggest that these surfaces are "invisible" to biological constituents in a manner tunable by the ionic environment and the chemical design of the zwitterionic surface.

Highly stable deep-blue emitting CsPbBr3 nanoplatelets with modified zwitterionic surface passivation

Two-dimensional CsPbBr3 nanoplatelets (NPLs) with narrow emission line width are one of the most promising materials for lighting and display applications. Nevertheless, it has been difficult to successfully synthesize deep-blue emitting CsPbBr3 NPLs with long-term stability and high photoluminescence quantum yield (PLQY), which prevents their widespread application in the field of lighting. The use of ligands engineering strategy has demonstrated an increase in the PLQY and stability. Herein, a method employing in situ formation of modified zwitterionic surface ligands is proposed to successfully synthesize high-quality CsPbBr3 NPLs. Zwitterionic passivation strategy can produce deep blue emission of CsPbBr3 NPLs at ∼ 461 nm, achieving a near-unity quantum yield and excellent stability for long-term storage at room-temperature, heat treatment, and ultraviolet irradiation. This enhancement can be attributed to the strong chelation between the modified zwitterions and the surface of CsPbBr3 NPLs, which can effectively immobilize surface halide ions and passivate surface defects. This work provides a flexible way to achieve high PLQY and improve the stability issues in perovskite NPLs.

Synergistic antibacterial and antifouling wound dressings: Integration of photothermal-activated no release and zwitterionic surface modification

Addressing the pervasive issue of bacteria and biofilm infections is crucial in the development of advanced antifouling wound dressings. In this study, a novel wound healing treatment using sulfobetaine (SBMA) decorated electrospun fibrous membrane based on polycaprolactone (PCL)/nitric oxide (NO) donors was developed. The fabrication involved a dual strategy, first integrating NO donors into mesoporous polydopamine (MPDA) and complexed with PCL/PEI to electrospin nanofibers. The fibrous membrane exhibited a potent antibacterial response upon irradiation at 808 nm, owing to a combination of NO and photothermal effect that effectively targets bacteria and disrupts biofilms. Surface functionalization of the membrane with PEI allowed for the attachment of SBMA via Michael addition, fabricating a zwitterionic surface, which significantly hinders protein adsorption and reduces biofilm formation on the wound dressing. In vitro and in vivo assessments confirmed the rapid bactericidal capabilities and its efficacy in biofilm eradication. Combining photothermal activity, targeted NO release and antifouling surface, this multifaceted wound dressing addresses key challenges in bacterial infection management and biofilm eradication, promoting efficient wound healing.

Cysteine-based antifouling superhydrophilic membranes prepared via facile thiol-ene click chemistry for efficient oil-water separation

Superhydrophilic membranes with underwater superoleophobicity for oil-water separation have been attracted widely attention. Nevertheless, oil contamination of such membranes represents a pressing challenge in this field. Superhydrophilic/underwater superoleophobic membranes with surface zwitterionic moieties are proved to show excellent antifouling properties; however, such zwitterionic surface modifiers adopted previously usually face the problem of cumbersome synthesis relying on expensive reagents and complicated procedures, accompanied with poor acid/alkali resistance due to the unstable linkers, restricting their practical applications. Herein, we describe an alternative strategy for fabricating antifouling superhydrophilic/underwater superoleophobic membranes from a natural amino acid. Sand particle-based sintered glass membranes were firstly coated with silicone nanofilaments using vinyltrichlorosilane as a precursor through chemical vapor deposition; and then the surfaces of silicone nanofilaments were further functionalized with cysteine via thiol-ene click chemistry. The resulting membranes exhibited high separation flux and efficiency for gravity-driven separation of various oil-water mixtures and surfactant-stabilized oil-in-water emulsions. Moreover, such membranes displayed excellent antifouling properties and were reusable for the separation of oil-water mixtures and surfactant-stabilized oil-in-water emulsions. With the advantages of facile fabrication, low-cost, fouling resistance and high separation performance, we believe that cysteine-based glass membranes without any hydrolytic bonds will arouse tremendous attentions for oil-water separation.

Quantum Yield Enhancement of Carbon Quantum Dots Using Chemical-Free Precursors for Sensing Cr (VI) Ions

Quantum yield illustrates the efficiency that a fluorophore converts the excitation light into fluorescence emission. The quantum yield of carbon quantum dots (CQDs) can be altered via precursors, fabrication conditions, chemical doping, and surface modifications. In this study, CQDs were first fabricated from whole-meal bread using a chemical-free hydrothermal route, and a low quantum yield (0.81%) was obtained. The combination of whole-meal bread, soybean flour, and lemon juice generated CQDs with almost four folds of enhancement in quantum yield. Detailed characterization suggested that these CQDs were subjected to more complete hydrothermal reactions and had zwitterionic surfaces. The CQDs could selectively detect Cr (VI) ions with a limit of detection (LOD) of 8 ppm. This study shows that the enhancement of the quantum yield of CQDs does not need chemicals, and it is achievable with food precursors.

Electrified Interactions of Polyzwitterions with Charged Surfaces: Role of Dipole Orientation and Surface Potentials.

The zwitterionic groups possess strong dipole moments, leading to inter- or intrachain interactions among zwitterionic polymers. This study aims to demonstrate the interaction of polyzwitterions poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), and poly(carboxybetaine methacrylate) (PCBMA) with electrified surfaces, despite their electrically neutral nature. We studied the adsorption of polyzwitterions and their monomers on electrified surfaces by using an electrochemical quartz crystal microbalance with dissipation (EQCM-D). The interaction between zwitterionic molecules and charged surfaces is explored by adjusting the surface potentials. Interestingly, the adsorption of polyzwitterions can be influenced by external potential, primarily due to the formation of polyzwitterions restricting the mobility of zwitterionic groups, affecting the adsorption behavior of polyzwitterions based on the surface potential. The impact is determined by the arrangement of positive and negative ions within the zwitterionic groups, which are the dipole orientation. Additionally, surface potentials determine the adsorption rate, amount, and chain conformation of the adsorbed thin polyzwitterion layers. The effect of ionic strength was investigated by introducing electrolytes into the aqueous solutions to assess the range of influenced surface potentials.

Zwitterionic stabilized water-borne polymer colloids for antifouling coatings

This study presents antifouling waterborne (meth)acrylic coatings prepared through seeded semi-continuous emulsion polymerization, using trace amounts of a zwitterionic monomer 2-(methacryloyloxy)ethyl dimethyl-(3-sulfopropyl)ammonium hydroxide (DMAPS). DMAPS was introduced with a dual purpose, to establish a protective layer of DMAPS containing polymer chains on the films' surface, thereby imparting antifouling characteristics, while simultaneously provides in-situ colloidal stability to the emulsion during polymerization.By providing colloidal stability to (meth)acrylic polymer particles in aqueous dispersion (latex), DMAPS-rich units are distributed on the surface of the polymer particles and subsequently on the surface of the resulting polymer films. Subsequent analysis revealed that the films exhibited diminished hydrophilicity, a more textured surface, and diminished affinity for water entrapment compared to conventionally stabilized (meth)acrylic films. Such surfaces demonstrated high resistance to fouling and weak adhesion of the studied BSA protein. These effects were positively influenced by the quantity of DMAPS incorporated within the (meth)acrylic films that allow higher coverage with DMAPS rich polymer chains.The proposed methodology not only emphasizes a potent pathway for the development of environmentally-conscious, waterborne film-forming coating technology but also involves the simultaneous integration of a zwitterionic surface layer, conveying remarkable antifouling attributes to the resulting (meth)acrylic coating film.

Comparison of Superhydrophilic, Liquid-Like, Liquid-Infused, and Superhydrophobic Surfaces in Preventing Catheter-Associated Urinary Tract Infection and Encrustation.

Over the past decade, superhydrophilic zwitterionic surfaces, slippery liquid-infused porous surfaces, covalently attached liquid-like surfaces, and superhydrophobic surfaces have emerged as the most promising strategies to prevent biofouling on biomedical devices. Despite working through different mechanisms, they have demonstrated superior efficacy in preventing the adhesion of biomolecules (e.g., proteins and bacteria) compared with conventional material surfaces. However, their potential in combating catheter-associated urinary tract infection (CAUTI) remains uncertain. In this research, we present the fabrication of these four coatings for urinary catheters and conduct a comparative assessment of their antifouling properties through a stepwise approach. Notably, the superhydrophilic zwitterionic coating demonstrated the highest antifouling activity, reducing 72.3% of fibrinogen deposition and over 75% of bacterial adhesion (Escherichia coli and Staphylococcus aureus) when compared with an uncoated polyvinyl chloride (PVC) surface. The zwitterionic coating also exhibited robust repellence against blood and improved surface lubricity, decreasing the dynamic coefficient of friction from 0.63 to 0.35 as compared with the PVC surface. Despite the fact that the superhydrophilic zwitterionic and hydrophobic liquid-like surfaces showed great promise in retarding crystalline biofilm formation in the presence of Proteus mirabilis, it is worth noting that their long-term antifouling efficacy may be compromised by the proliferation and migration of colonized bacteria as they are unable to kill them or inhibit their swarming. These findings underscore both the potential and limitations of these ultralow fouling materials as urinary catheter coatings for preventing CAUTI.

Milk exosomes anchored with hydrophilic and zwitterionic motifs enhance mucus permeability for applications in oral gene delivery.

Exosomes have emerged as a promising tool for the delivery of drugs and genetic materials, owing to their biocompatibility and non-immunogenic nature. However, challenges persist in achieving successful oral delivery due to their susceptibility to degradation in the harsh gastrointestinal (GI) environment and impeded transport across the mucus-epithelium barrier. To overcome these challenges, we have developed high-purity bovine milk exosomes (mExo) as a scalable and efficient oral drug delivery system, which can be customized by incorporating hydrophilic and zwitterionic motifs on their surface. In our study, we observed significantly improved transport rates by 2.5-4.5-fold in native porcine intestinal mucus after the introduction of hydrophilic and zwitterionic surface modifications, as demonstrated by transwell setup and fluorescence recovery after photobleaching (FRAP) analysis. Remarkably, mExo functionalized by a block peptide (BP), consisting of cationic and anionic amino acids arranged in blocks at the two ends, demonstrated superior tolerability in the acidic gastric environment (with a protein recovery rate of 84.8 ± 7.7%) and exhibited a 2.5-fold increase in uptake by intestinal epithelial cells. Furthermore, both mExo and mExo-BP demonstrated successful intracellular delivery of functional siRNA, resulting in up to 65% suppression of the target green fluorescence protein (GFP) gene expression at a low dose of siRNA (5 pmol) without causing significant toxicity. These findings highlight the immense potential of modifying mExo with hydrophilic and zwitterionic motifs for effective oral delivery of siRNA therapies.

Relationships between Water's Structure and Solute Affinity at Polypeptoid Brush Surfaces.

Excellent antifouling surfaces are generally thought to create a tightly bound layer of water that resists solute adsorption, and highly hydrophilic surfaces such as those with zwitterionic functionalities are of significant current interest as antifoulant strategies. However, despite significant proofs-of-concept, we still lack a fundamental understanding of how the nanoscopic structure of this hydration layer translates to reduced fouling, how surface chemistry can be tuned to achieve antifouling through hydration water, and why, in particular, zwitterionic surfaces seem so promising. Here, we use molecular dynamics simulations and free energy calculations to investigate the molecular relationships among surface chemistry, hydration water structure, and surface-solute affinity across a variety of surface-decorated chemistries. Specifically, we consider polypeptoid-decorated surfaces that display well-known experimental antifouling capabilities and that can be synthesized sequence specifically, with precise backbone positioning of, e.g., charged groups. Through simulations, we calculate the affinities of a range of small solutes to polypeptoid brush surfaces of varied side-chain chemistries. We then demonstrate that measures of the structure of surface hydration water in response to a particular surface chemistry signal solute-surface affinity; specifically, we find that zwitterionic chemistries produce solute-surface repulsion through highly coordinated hydration water while suppressing tetrahedral structuring around the solute, in contrast to uncharged surfaces that show solute-surface affinity. Based on the relationship of this structural perturbation to the affinity of small-molecule solutes, we propose a molecular mechanism by which zwitterionic surface chemistries enhance solute repulsion, with broader implications for the design of antifouling surfaces.

Silica-coated magnetic nanorods with zwitterionic surface functionalization to overcome non-specific protein adsorption

Anisotropic magnetic nanoparticles are receiving growing interest for biomedical applications due to their interesting properties, particularly for MRI and magnetic hyperthermia. In this work, a two-step, relatively simple synthesis pathway of magnetite nanorods was optimised. A ligand from the catechol family, known for its high iron oxide surface affinity, was used to transfer them into aqueous phase. The magnetite nanorods were then coated with a layer of fluorescent silica, whose surface was functionalised in two ways: either by short poly(ethylene glycol) (PEG) chains or by sulfobetaine zwitterionic molecules. A wide range of techniques were used to thoroughly characterise their physical structure, magnetic properties and dispersion characteristics. Finally, a study of the adsorption of a fluorescent model protein revealed that zwitterionic sulfobetaine molecules were more effective than PEG chains in limiting the non-specific adsorption of this protein.

Codelivery of CuS and DOX into Deep Tumors with Size and Charge-Switchable PAMAM Dendrimers for Chemo-photothermal Therapy.

Accurate targeting of therapeutic agents to specific tumor tissues, especially via deep tumor penetration, has been an effective strategy in cancer treatments. Here, we described a flexible nanoplatform, pH-responsive zwitterionic acylsulfonamide betaine-functionalized fourth-generation PAMAM dendrimers (G4-AB), which presented multiple advantages for chemo-photothermal therapy, including template synthesis of ultrasmall copper sulfide (CuS) nanoparticles and further encapsulation of doxorubicin (DOX) (G4-AB-DOX/CuS), long-circulating performance by a relatively large size and zwitterionic surface in a physiological environment, combined size shrinkage, and charge conversions via pH-responsive behavior in an acidic tumor microenvironment (TME). Accordingly, high tumor penetration and positive cell uptake for CuS and DOX have been determined, which triggered an excellent combination treatment under near-infrared irradiation in comparison to the monochemotherapy system and irresponsive chemo-photothermal system. Our study represented great promise in constructing multifunctional carriers for the effective delivery of photothermal nanoparticles and drugs in chemo-photothermal therapy.

PH-activated antibacterial coating switching from polyzwitterion to polycation

Stimuli-responsive surfaces have the potentials to solve the trade-off between biocompatibility and antibacterial performance by switching specific function on-demand, which makes them a promising option for developing biocompatible antibacterial surfaces. In this study, a pH-responsive antibacterial surface was created by grafting polycationic brushes and forming an acid-sensitive zwitterionic structure through a spontaneous amino-yne click reaction. Under physiological conditions, the zwitterionic structure provided the surface with good biocompatibility, as confirmed by lower hemolysis and cytotoxicity, as well as low adhesion and activation of platelets. When bacteria begin to colonize on the biomaterial surface, the decrease in local pH can break the acid-sensitive enamine bond and expose the polycations, activating the bactericidal activity. The good and on demand bactericidal activity was verified by the stimulated and authentic bacterial infection conditions. This study highlights the potential of stimuli-responsive zwitterionic surfaces as a valuable option for infection-resistant medical devices.

Cell-Selective Binding Zwitterionic Polymeric Micelles Boost the Delivery Efficiency of Antibiotics.

Effective accumulation and penetration of antibiotics in the biofilm are critical issues for bacterial infection treatment. Red blood cells (RBCs) have been widely utilized to hitchhike nanocarriers for drug delivery. It is vital and challenging to find a nanocarrier with an appropriate affinity toward RBCs and bacteria for selective hitchhiking and release that determines the drug delivery efficiency and specificity. Herein, we report a zwitterionic polymer poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate) (OPDEA)-based micelle, which can hitchhike on RBCs in blood and preferentially release in the infection site. We found that OPDEA could bind to the RBCs cell membrane via phospholipid-related affinity and transfer to Gram-positive bacteria due to nearly an order of magnitude stronger interaction with the bacteria cell wall. The zwitterionic surface and cell-wall affinity of OPDEA-based micelles also promote their penetration in biofilm. The clarithromycin-loaded OPDEA micelles show efficient drug delivery into the infection site, resulting in excellent therapeutic performance in both peritonitis and pneumonia models by intravenous or spray administration. This simple RBC-selective hitchhiking and releasing antibiotic delivery system provides a promising strategy for the design of antibacterial nanomedicines.

Zwitterionic polymers-armored amyloid-like protein surface combats thrombosis and biofouling

Proteins, cells and bacteria adhering to the surface of medical devices can lead to thrombosis and infection, resulting in significant clinical mortality. Here, we report a zwitterionic polymers-armored amyloid-like protein surface engineering strategy we called as “armored-tank” strategy for dual functionalization of medical devices. The “armored-tank” strategy is realized by decoration of partially conformational transformed LZM (PCTL) assembly through oxidant-mediated process, followed by armoring with super-hydrophilic poly-2-methacryloyloxyethyl phosphorylcholine (pMPC). The outer armor of the “armored-tank” shows potent and durable zone defense against fibrinogen, platelet and bacteria adhesion, leading to long-term antithrombogenic properties over 14 days in vivo without anticoagulation. Additionally, the “fired” PCTL from “armored-tank” actively and effectively kills both Gram-positive and Gram-negative bacterial over 30 days as a supplement to the lacking bactericidal functions of passive outer armor. Overall, this “armored-tank” surface engineering strategy serves as a promising solution for preventing biofouling and thrombotic occlusion of medical devices.

Engineering superstable islets-laden chitosan microgels with carboxymethyl cellulose coating for long-term blood glucose regulation in vivo

Islet transplantation to restore endogenous insulin secretion is a promising therapy for type 1 diabetes in clinic. However, host immune rejection seriously limits the survival of transplanted islets. Despite of the various encapsulation strategies and materials developed so far to provide immune isolation for transplanted islets, long-term blood glucose regulation is still difficult due to the inherent defects of the encapsulation materials. Herein, a novel islet-encapsulation composite material with low immunogenicity, good biocompatibility and excellent stability is reported. Specifically, chitosan (CS) microgels (diameter: ∼302 μm) are prepared via Michael addition reaction between maleimide grafted chitosan (CS-Mal) and thiol grafted chitosan (CS-NAC) in droplet-based microfluidic device, and then zwitterionic surface layer is constructed on CS microgel surface by covalent binding between maleimide groups on CS and thiol groups on thiol modified carboxymethyl cellulose (CMC-SH). The as-formed carboxymethyl cellulose coated chitosan (CS@CMC) microgels show not only long-term stability in vivo owing to the non-biodegradability of CMC, but also fantastic anti-adsorption and antifibrosis because of the stable zwitterionic surface layer. As a result, islets encapsulated in the CS@CMC microgels exhibit high viability and good insulin secretion function in vivo, and long-term blood glucose regulation is achieved for 180 days in diabetic mice post-transplantation.