Alginate (Alg) coatings have attracted attention as protective layers on solid surfaces for marine antifouling applications due to their strong water binding capability and environmentally friendly characteristics. However, the effectiveness of Alg coatings in preventing marine fouling diminishes upon interaction with divalent cations present in seawater. To address this issue, post-modification of the Alg coating is conducted. The carboxyl groups of Alg, which are susceptible sites for interaction with divalent cations, are conjugated with polymerization initiators through metal-mediated coordination bond formation. Subsequently, poly(sulfobetaine methacrylate) (poly(SBMA)) brushes are grown from the initiator-immobilized Alg coatings, resulting in the formation of multilayered Alg/poly(SBMA) coatings. In marine diatom adhesion assays using Amphora Coffeaeformis, multilayered Alg/poly(SBMA) coatings exhibited superior antifouling performance compared to single-layered Alg or poly(SBMA) coating controls.

Multifunctional hydrogel dressings are promising for wound healing. In the study, chlorhexidine(CHX) loaded double network hydrogels were prepared by free radical polymerization of sulfobetaine and oxidative self-crosslinking of reduced keratin. The introduced keratin and CHX endowed hydrogels with cytocompatibility, antioxidant capability as well as enhanced antibacterial activity due to the antifouling property of polysulfobetaine. These hydrogels exhibited acidity, glutathione(GSH), and trypsin triple-responsive release behaviors, resulting in the accelerated release of CHX under wound microenvironments. Intriguingly, the freeze-drying hydrogels could be ground to powders and sprinkled on the irregular wound bed, followed by absorbing wound fluid to reform hydrogel in situ. These xerogel powders were more convenient for sterilization, formulation, and storage. Further, these xerogel powders could be rejected after being mixed with an appropriate amount of water. In vivo infected wound healing confirmed that the xerogel powder dressing significantly promoted collagen deposition and reduced inflammation, thereby accelerating the closure and regeneration of skin wounds. Taken together, these degradable xerogel powders have great potential applications for wound healing.

Using the M13 phage display, a series of 7- and 12-mer peptides which interact with new sulfobetaine hydrogels are identified. Two peptides each from the 7- and 12-mer peptide libraries bind to the new sulfobetaine hydrogels with high affinity compared to the wild-type phage lacking a dedicated hydrogel binding peptide. This is the first report of peptides binding to zwitterionic sulfobetaine hydrogels and the study therefore opens up the pathway toward new phage or peptide/hydrogel hybrids with high application potential.

This article reviews the synthesis of polyzwitterions (PZs) (poly-carboxybetaines, -phosphonobetaines, and -sulfobetaines) having multiple pH-responsive centers. The synthesis follows the Butler cyclopolymerization protocol involving a multitude of diallylammonium salts and their copolymerization with SO2 and maleic acid. The PZs have been transformed into cationic-, anionic-polyelectrolytes, and polyampholytes under the influence of pH. Particular attention is given to the application of these polymers as antiscalants, mild steel corrosion inhibitors, components in constructing Aqueous Two-Phase Systems (ATPSs), and membrane modifiers. The ATPSs could be used to separate various biomolecules, including proteins. Many amphiphilic polymers incorporating a few mol % hydrophobic monomers have shown enhanced viscosities and could be suitable for applications in oil fields. The progress of applying Butler cyclopolymerization in reversible addition-fragmentation chain transfer (RAFT) chemistry has been discussed. Future works are expected to focus on RAFT cyclopolymerization to construct block copolymers.

Zwitterionic sulfobetaine-based monolithic stationary phases have attracted increasing attention for their use in hydrophilic interaction chromatography. In this study, a novel hydrophilic polymeric monolith was fabricated through photo-initiated copolymerization of 3-(3-vinyl-1-imidazolio)-1-propanesulfonate (SBVI) with pentaerythritol triacrylate using methanol and tetrahydrofuran as the porogenic system. Notably, the duration for the preparation of this novel monolith was as little as 5 min, which was significantly shorter than that required for previously reported sulfobetaine-based monoliths prepared via conventional thermally initiated copolymerization. Moreover, these monoliths showed good morphology, permeability, porosity (62.4%), mechanical strength (over 15 MPa), column efficiency (51,230 plates/m), and reproducibility (relative standard deviations for all analytes were lower than 4.6%). Mechanistic studies indicated that strong hydrophilic and negative electrostatic interactions might be responsible for the retention of polar analytes on the zwitterionic SBVI-based monolith. In particular, the resulting monolith exhibited good anti-protein adhesion ability and low nonspecific protein adsorption. These excellent features seem to favor its application in bioanalysis. Therefore, the novel zwitterionic sulfobetaine-based monolith was successfully employed for the highly selective separation of small bioactive compounds and the efficient enrichment of N-glycopeptides from complex samples. In this study, we prepared a novel zwitterionic sulfobetaine-based monolith with good performance and developed a simpler and faster method for preparation of zwitterionic monoliths.

The injective lyotropic liquid crystalline nanogels (LLCNs) were widely used in drug delivery systems. But when administered in vivo, LLCNs exposed to the biological environment interact with proteins. Recently, it has been shown that nanoparticles coated with zwitterions can inhibit their interaction with proteins. Thus, in this study, the interaction between proteins and LLCNs coated with the zwitterionic material sulfobetaine (GLLCNs@HDSB) was investigated using bovine serum albumin (BSA) as a model protein. Interestingly, it was found that GLLCNs@HDSB at higher concentrations (≥0.8 mg/mL) could block its interaction with BSA, but not at lower concentrations (<0.8 mg/mL), according to the results of ultraviolet, fluorescence, and circular dichroism spectra. In the ultraviolet spectra, the absorbance of GLLCNs@HDSB (0.8 mg/mL) was 1.9 times higher than that without the sulfobetaine coating (GLLCNs) after incubation with protein; the fluorescence quenching intensity of GLLCNs@HDSB was conversely larger than that of the GLLCNs; in circular dichroism spectra, the ellipticity value of GLLCNs@HDSB was significantly smaller than that of the GLLCNs, and the change in GLLCNs@HDSB was 10 times higher than that of the GLLCNs. Generally, nanoparticles coated with sulfobetaine can inhibit their interaction with proteins, but in this study, LLCNs showed a concentration-dependent inhibitory effect. It could be inferred that in contrast to the surface of nanoparticles covered with sulfobetaine in other cases, the sulfobetaine in this study interacted with the LLCNs and was partially inserted into the hydrophobic region of the LLCNs. In conclusion, this study suggests that coating-modified nanoparticles do not necessarily avoid interacting with proteins, and we should also study coating-modified nanoparticles interacting with proteins both in vitro and in vivo. In the future, finding a coating material to completely inhibit the interaction between LLCNs and proteins will generate a great impetus to promote the clinical transformation of LLCNs.

The grafting of zwitterionic molecules onto solid surfaces is an important tool for decreasing the unwanted adsorption of biomolecules, such as proteins, bacteria, and cells. This has been achieved through various approaches, such as zwitterionic monolayer/multilayer formation, surface-initiated polymerization of zwitterionic monomers, and grafting of presynthesized zwitterionic polymers. Recently, a coordination-driven approach to grafting zwitterionic polymers onto solid surfaces has been discovered to be an effective method because of its versatility and robustness. However, the bacterial adhesion resistance of zwitterionic polymer grafting has been explored using only one molecular weight, and the non-biofouling performance against other fouling organisms has remained unexamined. In this study, the characteristics of coordination-driven surface zwitteration are systematically investigated. Sulfobetaine (SB) polymers with three different molecular weights are synthesized and employed for surface grafting. Polydopamine is used as a surface primer, and SB polymers are grafted onto the surfaces via the formation of metal-mediated coordinate bonds. The effect of molecular weight on the grafting efficiency and non-biofouling performance is investigated via protein adsorption and marine diatom adhesion assays. The SB polymer with a high molecular weight is found to be crucial for achieving strong resistance to protein adsorption and marine fouling.

β-Cyclodextrins (β-CDs) and β-CD-containing polymers have attracted considerable attention as potential candidates for the treatment of cholesterol-related metabolic and intractable diseases. We have advocated the use of β-CD-threaded acid-degradable polyrotaxanes (PRXs) as intracellular delivery carriers for β-CDs. As unmodified PRXs are insoluble in aqueous solutions, chemical modification of PRXs is an essential process to improve their solubility and impart novel functionalities. In this study, we investigated the effect of the modification of zwitterionic sulfobetaines on PRXs due to their excellent solubility, biocompatibility, and bioinert properties. Sulfobetaine-modified PRXs were synthesized by converting the tertiary amino groups of precursor 2-(N,N-dimethylamino)ethyl carbamate-modified PRXs (DMAE-PRXs) using 1,3-propanesultone. The resulting sulfobetaine-modified PRXs showed high solubility in aqueous solutions and no cytotoxicity, while their intracellular uptake levels were low. To further improve this system, we designed PRXs cografted with zwitterionic sulfobetaine and cationic DMAE groups via partial betainization of the DMAE groups. Consequently, the interaction with proteins, intracellular uptake levels, and liver accumulation of partly betainized PRXs were found to be higher than those of completely betainized PRXs. Additionally, partly betainized PRXs showed no toxicity in vitro or in vivo despite the presence of residual cationic DMAE groups. Furthermore, partly betainized PRXs ameliorated the abnormal free cholesterol accumulation in Niemann-Pick type C disease patient-derived cells at lower concentrations than β-CD derivatives and previously designed PRXs. Overall, the cografting of sulfobetaines and amines on PRXs is a promising chemical modification for therapeutic applications due to the high cholesterol-reducing ability and biocompatibility of such modified PRXs. In addition, modification with both zwitterionic and cationic groups can be used for the design of various polymeric materials exhibiting both bioinert and bioactive characteristics.

This work demonstrates a cross-linkable zwitterionic polymer, the corresponding zwitterionic thermosetting resin, and their application for antifouling surface coating. The tertiary amine-containing benzoxazine group is utilized as a precursor to react with 1,3-propane sultone to introduce sulfobetaine moiety to benzoxazine group. The reaction route provides an effective approach for preparation of sulfobetaine-functionalized benzoxazines and the corresponding sulfobetaine-functionalized thermosetting resins of benzoxazines. The sulfobetaine-functionalized polybenzoxazine has been utilized as a coating material for ceramic porous membranes to impart protein-repelling characteristic to the membrane surface. In a filtration test on a Bovine serum albumin (BSA) aqueous solution, the sulfobetaine resin modified membrane shows a 96.2% of rejection rate and a 1680 ± 9 Lm2-h-1 of permeation flux at the first cycle test. In cycled measurements with membrane washing, the membrane shows a total flux decline ratio (Rt) and a reversible flux decline ratio (Rr) of about 46.9% and 43.1%, respectively. A high ratio of reversible fouling (Rr/Rt) of 91.9% is found, which supports the statement that the sulfobetaine-functionalized polybenzoxazine is an effective material to impart antifouling characteristic to porous materials for bioseparation and filtration.

This study quantified the interfacial forces associated with end-grafted, statistical (AB) co-polymers of sulfobetaine methacrylate (SBMA) and oligoethylene glycol methacrylate (OEGMA) (poly(SBMA-co-OEGMA)). Surface force apparatus measurements compared forces between mica and end-grafted copolymers containing 0, 40, or 80 mol% SBMA. Studies compared forces measured at low grafting density (weakly overlapping chains) and at high density (brushes). At high density, the range of repulsive forces did not change significantly with increasing SBMA content. By contrast, at low density, both the range and the amplitude of the repulsion increased with the percentage of SBMA in the chains. The ionic strength dependence of the film thickness and repulsive forces increased similarly with SBMA content, reflecting the increasing influence of charged monomers and their interactions with ions in solution. The forces could be described by models of simple polymers in good solvent. However, the forces and fitted model parameters change continuously with the SBMA content. The latter behavior suggests that ethyene glycol and sulfobetaine behave as non-interacting, miscible monomers that contribute independently to the interfacial forces. The results suggest that molecular scale properties of statistical poly (SBMA-co-OEGMA) films can be readily tuned by simple variation of the monomer ratios.