Protein-resistant Properties Research Articles

Fabrication of Antifouling/Antimicrobial Polysulfonium‐Coated Surface Against Biofilms and Water Bacterial Contamination

Bacterial attachment and colonization on the surface have caused a severe threat to human healthcare. The development of surface coatings with high antibacterial activity and low toxicity is highly desired. Herein, a series of sulfonium‐containing polypeptoids with various structural motifs on the side chains is synthesized, which are efficiently grafted on the silicone surface via plasma and ultraviolet light treatment. The resulting coating demonstrates excellent antibacterial properties against both Gram‐positive and Gram‐negative bacteria, as well as a sustained antibacterial effect at ambient temperature for up to one week. Moreover, the coating exhibits excellent in vitro antibiofilm and protein resistance properties, as well as excellent hemo/biocompatibility. Further, by fabricating a decontamination system with the coated substrates, the obtained coating materials show high efficiency in bacterial decontamination of water, which has great potential for use in water disinfection systems. All these results suggest that prepared coating with dual antibacterial and antifouling properties has great potential in combating bacterial contamination.

Laccase‐Triggered Surface Co‐Deposition of Gentisic Acid and Chitosan for Multifunctional Polymer Membranes

AbstractCo‐deposition of phenols and amines inspired by mussel‐inspired chemistry has attracted much attention in the field of surface and interface science and technology. However, most deposition systems are still limited to phenols with at least one catechol group. In this work, a novel enzyme‐triggered co‐deposition system based on a natural phenol (gentisic acid, GA) and a kind of biomacromolecule (chitosan, CS) is reported. With the catalysis of laccase, GA can be oxidized and further react with CS to form effective surface coatings on various substrates such as polypropylene microfiltration membrane (PPMM). The co‐deposition process takes only 40 min at room temperature and endows the membrane with superhydrophilicity and underwater superoleophobicity. The modified membranes show excellent separation performance, reusability, and long‐term stability for the separation of oil‐in‐water emulsions. The modified membranes are highly charged (pI ≈7.2) and capable of efficient dye adsorption. In addition, the modified membranes possess better protein resistance properties compared with the nascent membranes. This work demonstrates a green, mild, and highly efficient surface modification process based on laccase catalysis. The co‐deposition system comes from natural sources and expands the phenol family for constructing multi‐functional surface coatings.

Dual Optimized Sulfonated Polyethersulfone and Functionalized Multiwall Carbon Tube Based Composites High Fouling Resistance Membrane for Protein Separation.

Commercial grade sulfonated-Polyethersulfone (S-PES) and functionalized multiwall carbon nanotube (f-MWCNT)/polyvinylpyrrolidone (PVP) nanocomposites (NCs) were used to enhance and optimize the antifouling, protein resistance and protein separation properties of the S-PES ultrafiltration membranes. The polarities of sulfonic groups of S-PES, carbonyl carbon of pyrrolidone, hydroxyl and carboxyl groups of f-MWCNT in the membrane composition helped to strongly bind each other through hydrogen bonding, as shown by Fourier-transform infrared spectroscopy (FTIR). These binding forces greatly reduced the leaching of NCs and developed long finger-like projection, as confirmed by elution ratio and cross-sectional studies of the membranes via field emission scanning electron microscope (FESEM). The contact angle was reduced up to 48% more than pristine PES. Atomic force microscopy (AFM) was employed to study the various parameters of surface roughness with 3d diagrams, while grain analysis of membrane surface provided a quantitative estimation about volume, area, perimeter, length, radius and diameter. The NCs/S-PES enhanced the flux rate with an impressive (80–84%) flux recovery ratio and (58–62%) reversible resistance (Rr) value in situ, with 60% and 54.4% lesser dynamic and static protein adsorption. The best performing membrane were reported to remove 31.8%, 66.3%, 83.6% and 99.9% for lysozyme-(14.6 kDa), trypsin-(20 kDa), pepsin-(34.6 kDa) and bovine serum albumin (BSA-66 kDa), respectively.

Switchable [formula omitted]-lactoglobulin (BLG) adsorption on protein resistant oligo (ethylene glycol) (OEG) self-assembled monolayers (SAMs)

HypothesisAlthough protein adsorption at an interface is very common and important in biology and biotechnology, it is still not fully understood – mainly due to the intricate balance of forces that ultimately control it. In food processing (and medicine), controlling and manipulating protein adsorption, as well as avoiding protein adsorption (biofilm formation or membrane fouling) by the production of protein-resistant surfaces is of substantial interest. A major factor conferring resistance towards protein adsorption to a surface is the presence of tightly bound water molecules, as is the case in oligo ethylene glycol (OEG)-terminated self-assembled monolayers (SAMs). Due to strong attractive protein-protein and protein-surface interactions observed in systems containing trivalent salt ions, we hypothesize that these conditions may lead to a breakdown of protein resistance in OEG SAMs. ExperimentsWe studied the adsorption behavior of BLG in the presence of a lanthanum(III) chloride (LaCl3) at concentrations of 0, 0.1, 0.8 and 5.0 mM on normally protein resistant triethylene glycol-termianted (EG3) SAMs on a gold surface. We used quartz-crystal microbalance with dissipation (QCM-D) and neutron reflectivity (NR) to characterize the morphology of the interfacial region of the SAM. FindingsWe demonstrate that the protein resistance of the EG3 SAM breaks down beyond a threshold salt concentration c∗ and mirrors the bulk behaviour of this system, showing reduced adsorption beyond a second critical salt concentration c∗∗. These results demonstrate for the first time the controlled switching of the protein-resistant properties of this type of SAM by the addition of trivalent salt.

Superior anti-biofouling properties of mPEG-modified polyurethane networks via incorporation of a hydrophobic dangling chain

PEG-modification is a proven method to enhance the hydrophilicity, protein resistance, and anti-biofouling properties of polymer coatings. It is considered as the gold standard interfacial modification technique such that the higher PEG content, the higher hydrophilicity, and lower protein adsorption, i.e., the initial stage of the biofouling process. Nevertheless, increasing the PEG content causes a higher water uptake, which declines the polymer mechanical strength and increases its hydrolytic degradation rate. Thus, an effective strategy to produce a limited-water-absorbing PEG-modified polymer is to force the majority of PEG molecules to migrate towards the interfacial region while the modification takes place. In the current paper, we report the synthesis and characterization of crosslinked polycarbonate-based polyurethanes (PU) containing methoxy polyethylene glycol (mPEG) dangling chains. We show that the simultaneous incorporation of a limited amount of a low-surface-energy dangling chain, i.e., 1-octadecanol (oDEC), along with mPEG, results in a considerably higher mPEG surface concentration, according to X-ray photoelectron spectroscopy (XPS), and a significantly lower water contact angle (WCA), up to 45° lower. We also put forward a reasonable mechanism for our outstanding observation and verified it through extensive experiments, e.g., dynamic WCA, Atomic force microscopy (AFM), and XPS. Moreover, we outline a delicate dynamic WCA experimental protocol, by which the smart and responsive behavior of our coatings is illustrated. Eventually, we examined the mixed hydrophobic/hydrophilic dangling chains strategy for low-protein adsorption applications, in which a great potential has been discovered.

Reduction-Responsive Anticancer Nanodrug Using a Full Poly(ethylene glycol) Carrier.

Poly(ethylene glycol) (PEG) is applied extensively in biomedical fields because of its nontoxic, nonimmunogenic, and protein resistance properties. However, the strong hydrophilicity of PEG prevents it from self-assembling into an amphiphilic micelle in water, making it a challenge to fabricate a full-PEG carrier to deliver hydrophobic anticancer drugs. Herein, a paclitaxel (PTX)-loaded nanodrug was readily prepared through self-assembly of PTX and an amphiphilic PEG derivative, which was synthesized via melt polycondensation of two PEG diols (i.e., PEG200 and PEG10k) and mercaptosuccinic acid. The full PEG component endows the nanocarrier with good biocompatibility. Furthermore, because of the core cross-linked structure via the oxidation of mercapto groups, the nanodrug can be selectively disassociated under an intratumor reductive microenvironment through the reduction of disulfide bonds to release the loaded PTX and kill the cancer cells while maintaining high stability under the extratumor physiological condition. Additionally, it was confirmed that the nanodrug not only prolongs the biocirculation time of PTX but also possesses excellent in vivo antitumor efficacy while avoiding side effects of free PTX, for example, liver damage, which is promising for delivering clinical hydrophobic drugs to treat a variety of malignant tumors.

Low Fouling Peptides with an All (d) Amino Acid Sequence Provide Enhanced Stability against Proteolytic Degradation While Maintaining Low Antifouling Properties.

Peptide-functionalized surfaces, composed of optimized l-peptides, show a high resistance toward nonspecific adsorption of proteins. As l-peptides are known to be prone to proteolytic degradation, the aim of this work is to enhance the stability against enzymatic degradation by using the all d-peptide mirror image of the optimized l-peptides and to determine if the all d-enantiomer retains the protein-resistant and antifouling properties. Two l-peptides and their d-peptide mirror images, some of them containing the nonproteinogenic amino acid α-aminoisobutyric acid (Aib), were synthesized and tested against non-specific adsorption of the proteins lysozyme and fibrinogen and the settlement of marine diatom Navicula perminuta and marine bacteria Cobetia marina. Both the d-enantiomer and the insertion of Aib protected the peptides from proteolytic degradation. Protein resistance was enhanced with the d-enantiomers while maintaining the resistance toward diatoms.

Carboxybetaine functionalized nanosilicas as protein resistant surface coatings.

Materials with protein resistant properties are increasingly sought after for their potential application as low-fouling surface coatings. Hydrophilic coatings with improved resistance to protein fouling have been prepared from zwitterionic carboxybetaine (CB) functionalized silica nanoparticles (SiNPs). The authors report three methods of coating preparation via direct tethering of CB to predeposited particle films, a two-step surface functionalization process, and deposition of CB functionalized particle dispersions. The pH at which aqueous CB solutions were prepared and reacted to SiNPs was found to drastically influence the mechanism of CB attachment and affect the protein resistance of the resultant coatings. Depending on the method of coating preparation, protein binding to functionalized particle coatings was reduced by up to 94% compared to unfunctionalized SiNP control surfaces. As a result, all three methods offer simple and scalable fabrication routes for the generation of hydrophilic, zwitterionic interfaces with improved inhibition to protein fouling.

Design of comb-like poly(2-methyl-2-oxazoline) and its rapid co-deposition with dopamine for the study of antifouling properties

In this work, the comb-like poly(2-methyl-2-oxazoline) copolymer, poly(2-aminoethyl methacrylate-random-poly(2-methyl-2-oxazoline) (PMOXA-r-AEMA, PMA) is synthesized, and the CuSO4/H2O2-triggered dopamine/PMA co-deposition process is investigated. Ellipsometry, water contact angle (WCA), and X-ray photoelectron spectroscopy (XPS) are used to characterize the thickness, hydrophilicity, and surface composition of PMA-based coatings. PMA is facilely anchored to substrates within 60 min with the assistance of dopamine/polydopamine triggered by CuSO4/H2O2, and the coating thickness can achieve about 13 nm. Anti-protein adsorption and anti-blood platelet adhesion measurements are also studied to verify their antifouling properties. The adsorption capacity of FITC-BSA can be reduced to 5% of the original surface, and PMA-based coatings present excellent protein-resistant properties (∼95% reduction relative to gold surface) according to surface plasmon resonance (SPR) measurement, and it can resist adhesion of almost all blood platelets. Moreover, it is applied to a capillary inner wall for surface modification. An alkaline protein mixture and egg white proteins are successfully separated, and present excellent stability. The relative standard deviation (RSD) of migration time is lower than 0.71%. The practicability of this promising PMA-based coatings with this preparation strategy can be used for further proteomics analysis.

Protein Resistance Driven by Polymer Nanoarchitecture.

We report that the nanometer-scale architecture of polymer chains plays a crucial role in its protein resistant property over surface chemistry. Protein-repellent (noncharged), few nanometer thick polymer layers were designed with homopolymer chains physisorbed on solids. We evaluated the antifouling property of the hydrophilic or hydrophobic adsorbed homopolymer chains against bovine serum albumin in water. Molecular dynamics simulations along with sum frequency generation spectroscopy data revealed the self-organized nanoarchitecture of the adsorbed chains composed of inner nematic-like ordered segments and outer brush-like segments across homopolymer systems with different interactions among a polymer, substrate, and interfacial water. We propose that this structure acts as a dual barrier against protein adsorption.

New protein-resistant surfaces of amphiphilic graft copolymers containing hydrophilic poly(ethylene glycol) and low surface energy fluorosiloxane side-chains

Methacryloyl-terminated poly[methyl(3,3,3-trifluoropropyl)siloxane] (PMTFPS-MA) macro-monomers with controlled segment length were designed and synthesized by anionic ring-opening polymerization of 1,3,5-trimethyl-1,3,5-tri(3′,3′,3′-trifluoropropyl)cyclotrisiloxane (F3). Then, a series of novel amphiphilic fluorosiloxane-containing graft copolymers were prepared using PMTFPS-MA, poly(ethylene glycol) methyl ether methacrylate (PEG-MA) and methyl methacrylate (MMA) as the co-monomers, and their surface properties and protein-resistant performance were investigated. It was found that the composition of amphiphilic graft copolymers would play an important role in the protein-resistant properties. When the copolymers contain 65.5 wt% PEO segments and 6.4 wt% PMTFPS segments, the coating surface exhibits strong protein-resistant property and shows almost no protein adsorption on it. Based on the surface analysis of amphiphilic graft copolymer films both in dry and wet conditions, the protein-resistant property of amphiphilic copolymers can be owing to the transition from a hydrophobic surface to hydrophilic surface with highly efficient water-driven PEO surface migration. The PEO segments are utilized to prevent protein adsorption whereas the low surface energy PMTFPS segments are utilized to drive away the adsorbed proteins.

Protein-resistant properties of poly(N-vinylpyrrolidone)-modified gold surfaces: The advantage of bottle-brushes over linear brushes

Poly(N-vinylpyrrolidone) (PVP)-modified surfaces have been shown to possess excellent protein resistance and good biocompatibility. However, PVP-modified surfaces with different molecular architectures have not been prepared, and their protein-resistant properties have not been studied. Herein, gold surfaces modified with linear PVP brush and PVP bottle-brush architectures were prepared by photoinitiated surface grafting polymerization. Ellipsometry, X-ray photoelectron spectroscopy (XPS), water contact angle, Fourier transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM) were utilized to characterize the prepared surfaces. The protein-resistant properties were investigated by a quartz crystal microbalance with dissipation (QCM-D) with bovine serum albumin (BSA), fibrinogen (Fg) and lysozyme (Lyz). Compared with the ungrafted QCM-D chips, the PVP bottle-brush-grafted chips (9.3 nm thickness) showed superior protein resistance over linear PVP brush-grafted chips (9.9 nm thickness). Furthermore, the PVP bottle-brushes reduced the levels of BSA, Fg and Lyz adsorption by 97%, 85% and 69%, respectively. Moreover, to demonstrate potential applications as functional biosensors and in the biomedical field, PVP bottle-brushes containing glycopolymer-grafted gold surfaces were fabricated. Laser scanning confocal microscopy (LSCM) demonstrated that these glycopolymer surfaces showed excellent protein resistance and specific ConA binding ability. Overall, we speculate that the data presented here can provide useful information for the development of excellent antifouling materials and functional biosensors.

Surface Density Variation within Cyclic Polymer Brushes Reveals Topology Effects on Their Nanotribological and Biopassive Properties

While topology effects by cyclic polymers in solution and melts are well-known, their translation into the interfacial properties of polymer "brushes" provides new opportunities to impart enhanced surface lubricity and biopassivity to inorganic surfaces, above and beyond that expected for linear analogues of identical composition. The impact of polymer topology on the nanotribological and protein-resistance properties of polymer brushes is revealed by studying linear and cyclic poly(2-ethyl-2-oxazoline) (PEOXA) grafts presenting a broad range of surface densities and while shearing them alternatively against an identical brush or a bare inorganic surface. The intramolecular constraints introduced by the cyclization provide a valuable increment in both steric stabilization and load-bearing capacity for cyclic brushes. Moreover, the intrinsic absence of chain ends within cyclic adsorbates hinders interpenetration between opposing brushes, as they are slid over each other, leading to a reduction in the friction coefficient (μ) at higher pressures, a phenomenon not observed for linear grafts. The application of cyclic polymers for the modification of inorganic surfaces generates films that outperform both the nanotribological and biopassive properties of linear brushes, significantly expanding the design possibilities for synthetic biointerfaces.

Protein-Resistant Property of Egg White Ovomucin under Different pHs and Ionic Strengths.

Ovomucin is a mucin-type glycoprotein accounting for 3.5% (w/w) of total egg white proteins. The purpose of the study was to explore the potential of ovomucin as a protein-resistant material. Using bovine serum albumin (BSA) as a model protein, ovomucin decreased the fluorescence intensities of the adsorbed BSA from 10.90 ± 2.18 to 0.67 ± 0.75, indicating its protein-resistant property. To understand the underlying mechanism, pure repulsive forces between ovomucin and model proteins (e.g., BSA and ovomucin) at various pHs (2.0, 6.0, and 7.2) and ionic strengths (0.1, 10, and 150 mM NaCl) were measured using a surface forces apparatus. Further studies by using atomic force microscope imaging, zeta potential, and dynamic light scattering suggested that the protein-resistant property of ovomucin was mainly attributed to strong electrostatic and steric repulsions between protein layers. This work has demonstrated that ovomucin has antifouling potential with broad applications in the areas of food processing industry and biomedical implants.

Improved antifouling ability of thin film composite polyamide membrane modified by a pH-sensitive imidazole-based zwitterionic polyelectrolyte

In this work, poly[1-vinyl-3(2-carboxyethyl) imidazolium betaine] (PVCIB), as a zwitterionic polyelectrolyte, was tethered onto a commercial thin film composite polyamide (TFC PA) membrane. First, polyvinyl imidazole (PVI) was grafted onto the TFC PA membrane surface by free radical graft polymerization method at various grafting times. Afterwards, one of PVI-modified membranes was betainized using 3-bromopropionic acid to obtain PVCIB brushes on the membrane surface. Evaluation of membrane performance through desalination process indicated that despite decrease of salt rejection, water flux increased from 73.4 L/m2 h in the PA membrane to 91.6 L/m2 h in the PA-PVCIB membrane. Antimicrobial assessment using Escherichia coli showed that the PVCIB-modified membrane was able to inhibit bacterial growth by about 98.8%. Antifouling and cleaning abilities of membranes were investigated using BSA and lysozyme at various pH values. It was revealed that hydrophilic PVCIB brushes considerably improved protein-resistant property of the TFC PA membrane. However, by considering pH-dependent behavior of PVCIB (zwitterionic at alkaline pH or polyelectrolyte at acidic pH), it was found that hydration repulsion or electrostatic repulsive forces also made a major contribution to the fouling mitigation. Accordingly, the PA-PVCIB membrane exhibited remarkable antifouling ability to resist non-specific protein adsorption at neutral and alkaline pHs, whereas both PA-PVI and PA-PVCIB membranes exhibited high resistance to the positively charged lysozyme adhesion at acidic pH.

The detection of brucellosis antibody in whole serum based on the low-fouling electrochemical immunosensor fabricated with magnetic Fe3O4@Au@PEG@HA nanoparticles

It is a novel competitive challenge for electrochemical biosensor to directly, rapidly and ultrasensitively detect the disease markers in the whole serum due to biofouling caused by the complexity of actual samples. In this paper, poly (ethylene glycol) (PEG) and hyaluronic acid (HA) were utilized to modify Fe3O4 @Au nanoparticles (NPs). Based on the successfully preparation and characterization of Fe3O4 @Au@PEG@HA NPs with TEM, SEM, XRD, FTIR and EDS, respectively, a novel immunosensor of brucellosis with high selectivity, sensitivity and almost perfect protein-resistant properties in various external environments, especially, in complex biological systems was fabricated. More importantly, this immunosensor is capable of assaying brucellosis antibody in 100% serum without suffering from any significant biological interference. In addition, a wide linear response range from 10–15 g mL−1 to 10–11 g mL−1 towards antibody in 100% serum and a low limit of detection (LOD) of 0.36 fg mL−1 (3σ, n = 13) are demonstrated, which indicates that this immunosensor has a promising potential in clinical diagnosis.

Poly(l-glutamic acid)-g-poly(ethylene glycol) external layer in polyelectrolyte multilayer films: Characterization and resistance to serum protein adsorption.

Formation of protein-resistant surfaces is a major challenge in the design of novel biomaterials and an important strategy to prevent protein adsorption is the formation of protein-resistant coatings. It can be achieved by proper modification of surfaces, e.g., by immobilization of hydrophilic polymers such as poly(ethylene glycol) (PEG). An appropriate method to immobilize PEG at charged surfaces is the adsorption of copolymers with PEG chains grafted onto polyelectrolyte backbone. The growing interest in the use of polyelectrolyte multilayer coatings in biomedical applications to improve biocompatibility and/or to prepare coating with antiadhesive properties has been the main reason for these studies. Therefore the aim was to produce protein resistant polyelectrolyte multilayer films. They were formed via the layer-by-layer approach, while their pegylation by the deposition of pegylated polyanion, PGA-g-PEG, as an external layer. The influence of PEG chain length and grafting density of PGA-g-PEG copolymers on the protein antiadhesive properties of pegylated polyelectrolyte multilayer films was investigated. To monitor the formation of pegylated and non-pegylated multilayer films, adsorption of the following proteins: HSA, Fibrinogen, and FBS were measured by quartz crystal microbalance (QCM - D). We found that protein adsorption onto all pegylated polyelectrolyte multilayers was significantly reduced in comparison to non-pegylated ones. Long-term performance tests confirmed the stability and the durability of the protein resistant properties of the pegylated multilayers. Antiadhesive properties of tested surfaces pegylated by PGA-g-PEG were compared to the available data for pegylated polycation PLL-g-PEG.

Preparation and characterization of poly dimethylsiloxane based on polyurethane hydrogels with interpenetrating network structure for contact lenses uses

The interpenetrating polymer network (IPN) silicone hydrogels have been synthesized using polydimethylsiloxane- polyurethane- polyethylene glycol methacrylate (PDMS–PU–PEGMA) prepolymer with different concentrations of N,N dimethyl acrylamide (DMA), polyethylene glycol methacrylate (PEGMA) and methacryloxypropyl tris(trimethylsoloxy)silane (TRIS) by UV initiated polymerization process in the presence of free radical photoinitiator. The physicomechanical and chemical properties of the IPN silicone hydrogels, as water content, protein resistance, contact angle, optical transparency and mechanical properties were evaluated. The results revealed that DMA and PEGMA incorporated in IPN silicone hydrogel improves the hydrophilicity of silicone hydrogel with higher optical transparency and better protein resistance ability. The moduli of IPN silicone hydrogels indicate stiffer network as the concentration of PDMS–PU–PEGMA prepolymer increased. IPN silicone hydrogels belong to hydrophilic surfaces with the lowest water contact angle of 48.76o.

Effect of End-Grafted Polymer Conformation on Protein Resistance.

Monte Carlo simulation combined with an experimental method was used to investigate the effect of the conformational structure of polymer brushes on their protein resistance. The end-grafted polymers with two conformational structures, i.e., linear and looped, were considered. Protein adsorption behaviors on the surfaces grafted with either linear or looped polymers were investigated. Different chain lengths and grafting numbers of end-grafted polymers were employed in this simulation. The simulation results indicated that for long polymer brushes the conformational change from linear to looped generally improved their protein-resistant property for all of the grafting numbers investigated here, and a remarkable improvement in protein resistance can be achieved at a certain grafting number. Moreover, the simulations revealed that the smoothness of the surface and the formation of a dense impenetrable layer are the two significant characteristics of the looped polymer brush in resisting protein adsorption. Meanwhile, experiment results also showed that for a given chain length and grafting number the protein-resistant property of the looped polymer brush was superior to that of the surface grafted with linear polymers, which is quite consistent with the simulation results. These results further elucidated the difference in the protein-resistant property between the linear and looped polymer brushes, which provided useful information for preparing excellent antifouling materials in future experiments.

Preparation of hydrophilic polymer brushes magnetic microspheres by surface-initiated for magnetic dispersive solid phase extraction of tetracycline antibiotic residues from honey

Activators regenerated by electron transfer-atom transfer radical polymerization (ARGET-ATRP) was applied to the continuous grafting of polybasic polymers and poly(ethylene glycol) (PEG) brushes on the surface of the magnetic microspheres (MMs). At first, the MMs were coated with silica gel, modified by amino group, and then 2-bromoisobutyryl bromide was grafted on the surface of MMs. After that, the hydrophilic polymer brushes magnetic microspheres (HMMs) were prepared by polymerization on the surface of the MMs. HMMs were characterized by transmission electron microscope (TEM) and Fourier transform-infrared (FT-IR) spectrometer. The adsorption performance to protein was studied. The results demonstrated that HMMs have the relatively uniform particle size, good dispersity and excellent protein resistance properties. Tetracycline antibiotics (TCs, tetracycline hydrochloride, chlortetracycline hydrochloride and doxycycline hydrochloride) in honey samples were determined by magnetic dispersion solid phase extraction (MDSPE) using the prepared HMMs and high performance liquid chromatography (HPLC). The average recoveries were obtained in the range of 85.8%-94.5%. The limits of detection (LODs) and limits of quantification (LOQs) of the proposed method were in the ranges of 1.92-2.56 μg/kg and 6.40-8.53 μg/kg, respectively. The proposed method was successfully applied to fast clean-up and enrichment of the TCs residues in honey.