Synergy between Zwitterionic Polymers and Hyaluronic Acid Enhances Antifouling Performance

Abstract

Challenges associated with nonspecific adsorption of proteins on sensor surfaces have steered the development of novel antifouling materials and strategies. Inspired by human synovial fluid composition and structure, we designed synergistic antifouling coatings with mixtures of hyaluronic acid (HA) and a zwitterionic bottlebrush polymer (BB). Using a fast and convenient online surface modification method, the polymers were immobilized on the Au surface, significantly increasing its hydrophilicity. Using surface plasmon resonance (SPR), a 10:1 ratio of HA to BB was found optimal to provide the best antifouling performance. Bovine serum albumin (BSA) adsorption on HA-BB coated surfaces was 0.2 ng/cm2, which was 60 times lower than BB or HA alone and 25 times lower than the commonly accepted ultralow adsorption limit (<5 ng/cm2), demonstrating the synergistic effect of HA and BB against nonspecific protein adsorption. This was found to be independent of BSA concentration up to physiological concentrations. Furthermore, the antifouling performance of HA-BB coated surfaces was tested against milk and serum, showing almost 92% lower protein adsorption than that on bare surfaces, suggesting the potential efficacy of this antifouling coating in real life settings.

Self-Assembled Nanogels Based on Ionic Gelation of Natural Polysaccharides for Drug Delivery

“…However, disadvantages also existed for each specific PS NG in the drug delivery. The hydrophilic HA itself has an antifouling property, and meanwhile, it could mediate a targeted delivery of drugs to the tumor with CD44 overexpression (Xia et al, 2019;Lee et al, 2020). However, most of the HA NP are retained in the endolysosomes following the trafficking of HA, which largely prevents the delivered drugs to access their molecular targets and subsequently limits the final therapeutic efficacy.…”

Low-Fouling Substrates for Plasmonic Sensing of Circulating Biomarkers in Biological Fluids

“…The functionalization with hyaluronic acid provides inert and stable ultralow-fouling surfaces (3 ng cm −2 ) thanks to the hydration layers formed by the amide and carboxyl groups of the disaccharide unit [41,55]. Several surface chemistries consisting of hyaluronic-acid-modified sensor chips have been proven to reduce protein adsorption (0.6-16.1 ng cm −2 ) in complex media when using hyaluronic acid in combination with alkanethiol or polydopamine films [36,56]. However, the antifouling capabilities of polysaccharide-based layers in both single-protein and complex systems are lower than those of PEG or zwitterionic coatings, and their use still remains focused on the functionalization of sensing surfaces.…”

“…To overcome this problem, antifouling materials have been developed in order to prevent the interference of undesired molecular Although the versatility of nanoplasmonic biosensing has permitted label-free detection of multiple biomarkers in biofluids at low detection levels, many plasmonic applications are still limited by nonspecific adhesion of proteins and cell matrices. To overcome this problem, antifouling materials have been developed in order to prevent the interference of undesired molecular interactions [34][35][36][37]. Therefore, the design of antifouling coatings is of paramount importance for preserving the long-term stability of bioactive nanosurfaces in complex biological media.…”

Low-fouling CNT-PEG-hydrogel coated quartz crystal microbalance sensor for saliva glucose detection

“…To circumvent these limitations, a host of anti-fouling materials have been developed to resist protein adsorption. Those commonlyapplied anti-fouling materials include poly(ethylene glycol) (PEG) and its derivatives, [28][29][30] zwitterionic materials, 31 bovine serum albumin (BSA), 32 peptides, 33 and other candidates (e.g., hyaluronic acid (HA), 34 polyoxazoline, 35 etc.). Compared to these antifouling materials, PEG and its derivatives are some of the most accessible and adopted materials, which tend to hydrate and form a hydrophilic surface that generates a large entropic penalty by releasing and displacing its bound water so as to resist the non-specic adsorption of proteins.…”