Ultralow‐Fouling, Functionalizable, and Hydrolyzable Zwitterionic Materials and Their Derivatives for Biological Applications

Abstract

In recent years, zwitterionic materials such as poly(carboxybetaine) (pCB) and poly(sulfobetaine) (pSB) have been applied to a broad range of biomedical and engineering materials. Due to electrostatically induced hydration, surfaces coated with zwitterionic groups are highly resistant to nonspecific protein adsorption, bacterial adhesion, and biofilm formation. Among zwitterionic materials, pCB is unique due to its abundant functional groups for the convenient immobilization of biomolecules. pCB can also be prepared in a hydrolyzable form as cationic pCB esters, which can kill bacteria or condense DNA. The hydrolysis of cationic pCB esters into nonfouling zwitterionic groups will lead to the release of killed microbes or the irreversible unpackaging of DNA. Furthermore, mixed-charge materials have been shown to be equivalent to zwitterionic materials in resisting nonspecific protein adsorption when they are uniformly mixed at the molecular scale.

Structures and Synthesis of Zwitterionic Polymers

“…A number of the large reviews have mostly descriptive character, confining themselves to an enumeration of the literature published [52,53]. The majority of reviews dealing with polyzwitterions have focused on one specific aspect, such as synthetic phosholipid polymers [21,[29][30][31][32]54], membranes [55], or on ultralow-fouling behaviour [27,38]. In particularly, the synthesis of polyzwitterions has been hardly treated systematically, as shall be done here.…”

“…Also, the RGD (arginine-glycine-aspartic acid) tripeptide motif that plays a key role in cell adhesion [26] represents a zwitterionic unit under physiological conditions. Thus not surprisingly, many polyzwitter-ions have been shown to be highly biocompatible [21,27,28], combining strong hydrophilicity with zero net charge and high salt tolerance. In an extension of this reasoning, much interest has focused on polyzwitterions for mimicking cell membranes [29][30][31][32] and for preparing tailored surfaces, as they can confer excellent lubrication [33][34][35] and excellent resistance to (bio)fouling to various materials [27,28,[36][37][38][39][40][41].…”

Hydration and Chain Entanglement Determines the Optimum Thickness of Poly(HEMA-co-PEG10MA) Brushes for Effective Resistance to Settlement and Adhesion of Marine Fouling Organisms

“…14,26 Some properties of hydrophilic materials, such as softness and strong hydration are considered important for effective antifouling or low adhesion by fouling species. With regard to how the antifouling properties depend of coating thickness, this has been studied for protein adsorption in a number of systems, including early and fundamental work on poly(ethylene glycol) (PEG) coatings, [27][28] and more recent work on both hydrophilic and zwitterionic polymers.…”

Use of Methionine Alkylation to Prepare Cationic and Zwitterionic Block Copolypeptide Vesicles

“…However, extruded zwitterionic M C 65 (L 0.5 /F 0.5 ) 20 vesicles were found to be non-toxic to HeLa cells at concentrations up to 100 µg/mL (Figure 3), similar to properties observed with other zwitterionic polymer systems. [19] These results show that although potentially toxic cationic sulfonium groups are introduced via M alkylation, these effects can be eliminated by simultaneous introduction of charge neutralizing functionality, as in the case of carboxymethylation. …”