Recent Developments in the Design of Non-Biofouling Coatings for Nanoparticles and Surfaces.

Biofouling is a major issue in the field of nanomedicine and consists of the spontaneous and unwanted adsorption of biomolecules on engineered surfaces. In a biological context and referring to nanoparticles (NPs) acting as nanomedicines, the adsorption of biomolecules found in blood (mostly proteins) is known as protein corona. On the one hand, the protein corona, as it covers the NPs' surface, can be considered the biological identity of engineered NPs, because the corona is what cells will "see" instead of the underlying NPs. As such, the protein corona will influence the fate, integrity, and performance of NPs in vivo. On the other hand, the physicochemical properties of the engineered NPs, such as their size, shape, charge, or hydrophobicity, will influence the identity of the proteins attracted to their surface. In this context, the design of coatings for NPs and surfaces that avoid biofouling is an active field of research. The gold standard in the field is the use of polyethylene glycol (PEG) molecules, although zwitterions have also proved to be efficient in preventing protein adhesion and fluorinated molecules are emerging as coatings with interesting properties. Hence, in this review, we will focus on recent examples of anti-biofouling coatings in three main areas, that is, PEGylated, zwitterionic, and fluorinated coatings.

Effect of Molecular Weights on Metal-Mediated Grafting of Sulfobetaine Polymers onto Solid Surfaces for Non-Biofouling Applications.

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.

Potentiometric Performance of Ion-Selective Electrodes Based on Polyaniline and Chelating Agents: Detection of Fe2+ or Fe3+ Ions.

We constructed a sensor for the determination of Fe2+ and/or Fe3+ ions that consists of a polyaniline layer as an ion-to-electron transducer; on top of it, chelating molecules are deposited (which can selectively chelate specific ions) and protected with a non-biofouling poly(2-methyl-2-oxazoline)s layer. We have shown that our potentiometric sensing layers show a rapid response to the presence of Fe2+ or Fe3+ ions, do not experience interference with other ions (such as Cu2+), and work in a biological environment in the presence of bovine serum albumin (as a model serum protein). The sensing layers detect iron ions in the concentration range from 5 nM to 50 µM.

Backfilling-Free Strategy for Biopatterning on Intrinsically Dual-Functionalized Poly[2-Aminoethyl Methacrylate-co-Oligo(Ethylene Glycol) Methacrylate] Films.

We demonstrated protein and cellular patterning with a soft lithography technique using poly[2-aminoethyl methacrylate-co-oligo(ethylene glycol) methacrylate] films on gold surfaces without employing a backfilling process. The backfilling process plays an important role in successfully generating biopatterns; however, it has potential disadvantages in several interesting research and technical applications. To overcome the issue, a copolymer system having highly reactive functional groups and bioinert properties was introduced through a surface-initiated controlled radical polymerization with 2-aminoethyl methacrylate hydrochloride (AMA) and oligo(ethylene glycol) methacrylate (OEGMA). The prepared poly(AMA-co-OEGMA) film was fully characterized, and among the films having different thicknesses, the 35 nm-thick biotinylated, poly(AMA-co-OEGMA) film exhibited an optimum performance, such as the lowest nonspecific adsorption and the highest specific binding capability toward proteins.

Non-biofouling property of well-defined concentrated polymer brushes.

The non-biofouling properties of polymer brushes of poly(2-hydroxyethyl methacrylate) (PHEMA), poly(2-hydroxyethyl acrylate) (PHEA), and poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA) were comprehensively studied by varying graft densities (i.e., semi-dilute and concentrated regimes) and the thicknesses at the dry state of 2 and 10 nm. Semi-dilute polymer brushes (SDPBs) were prepared by grafting-to method and concentrated polymer brushes (CPBs) were prepared by surface-initiated atom transfer radical polymerization (SI-ATRP). The adsorptions of proteins with different sizes were investigated on the brushes by quartz crystal microbalance (QCM) from a view point of size-exclusion effect specific to the CPBs. We confirmed that due to the size exclusion effect, the CPBs of all the three much suppressed proteins adsorption and human umbilical vein endothelial cell (HUVEC) adhesion compared with the corresponding SDPBs. In order to investigate what type of proteins adsorbed on the brushes to trigger cell adhesion, we identified adsorbed proteins from fetal bovine serum on the brushes using a high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Proteins were only detected on the SDPBs. Interestingly, the number and type of identified proteins were different on the SDPBs, indicating that chemical composition of the SDPBs affects protein adsorption, hence the cell adhesion. The adsorption mechanism on the SDPBs could be due to the combination of protein-polymer interaction and physical inclusion, whereas CPBs exhibit size exclusion effect combined with neutral hydrophilic nature of polymer, thereby, that provides excellent non-biofouling property.

Direct patterning and biofunctionalization of a large-area pristine graphene sheet.

Direct patterning of streptavidin and NIH 3T3 fibroblast cells was successfully achieved over a large-area pristine graphene sheet on Si/SiO2 by aryl azide-based photografting with the conventional UV lithographic technique and surface-initiated, atom transfer radical polymerization of oligo(ethylene glycol) methacrylate.