Aqueous Precipitation Polymerization Research Articles

Insights of mechanism and kinetics of acrylonitrile aqueous precipitation polymerization

Aqueous precipitation polymerization is commonly used in the industry due to its efficient heat dissipation, reaction stability and production flexibility. However, its mechanisms and kinetics are still partially unclear. The ammonium persulfate-ammonium sulfite monohydrate (APS-AS) initiated aqueous phase precipitation polymerization of acrylonitrile (AN) at low concentration was deeply investigated, with the APS initiation system as a control. The apparent kinetic equations for the APS and APS-AS initiation systems were determined to be Rp= K[AN]1.706[(NH4)2S2O8]0.704 and Rp= K[AN]3[(NH4)2S2O8]0.704[(NH4)2S2O3]−1.055, respectively. Monitoring AN distribution in the aqueous and polyacrylonitrile (PAN) phases revealed a rapid transition of the reaction site from the aqueous phase to the PAN phase following polymer precipitation. Zeta potential and primary particle number exposed that the nucleation site disparities between initiation systems led to different predominant factors affecting the polymerization rate. The change in molecular weight during polymerization had a maximum due to its dependence on the monomer concentration. The crystallinity of the product initially increased during polymerization, then decreased and eventually stabilized. Scanning electron microscopy (SEM) revealed that the diameter of the internal particles was larger, while the surface particles were smaller after coagulation. These findings offer crucial insights for optimizing aqueous precipitation polymerization and PAN particle property control.

Machine-learning-assisted prediction of the size of microgels prepared by aqueous precipitation polymerization.

The size of soft colloids (microgels) is essential; however, control over their size has typically been established empirically. Herein, we report a linear-regression model that can predict microgel size using a machine learning method, sparse modeling for small data, which enables the determination of the synthesis conditions for target-sized microgels.

A method for synthesis of oriented epitope-imprinted open-mouthed polymer nanocapsules and their use for fluorescent sensing of target protein

Epitope imprinting has proved to be an effective way for fabricating artificial receptors for protein recognition. Surface imprinting over sacrificial supports is particularly favorable for generating high-quality epitope-imprinted cavities, but obtaining nanomaterials by this way is still a challenge. Herein, we propose a method for the synthesis of oriented surface epitope-imprinted open-mouthed polymer nanocapsules (OM-MIP NCs) by sacrificing asymmetric template-modified Janus nanocores. Amine/aldehyde functionalized SiO2 Janus nanoparticles were prepared via the molten-wax-in-water Pickering emulsion approach, an easy scale-up technique. Epitope templates and vinyl groups were coupled to the aldehyde-bearing major side, whereas polyethylene glycol (PEG) chains were grafted to the amine-modified side. Incomplete imprinted shells were then generated principally on the non-PEGylated side via aqueous precipitation polymerization, hence affording OM-MIP NCs after etching the SiO2 nanocores. With a C-terminus nonapeptide of bovine serum albumin (BSA) chosen as a model epitope and polymerizable carbon dots added to the pre-polymerization solution, fluorescent OM-MIP NCs were synthesized for sensing of BSA. Such NCs reached maximal fluorescent response within 15 min, greatly faster than the closed imprinted NCs within 130 min, proving good accessibility of their inner-surface imprinted cavities thanks to the open mouths. Furthermore, they showed excellent target protein detection performance, with an imprinting factor of 7.8, a limit of detection of 43.8 nM and a linear range of 0.2–6 μM. The recoveries in bovine serum samples at four spiking levels ranged from 99.2 to 107.2%, with relative standard deviations of 1.2–5.9%.

Zwitterionic nanogels with temperature sensitivity and redox-degradability for controlled drug release

Zwitterionic polymers play an attractive role in the application of stealthy nanocarriers for their excellent antifouling property. Herein, a zwitterionic nanogel with temperature sensitivity and redox-responsive degradability prepared by copolymerization of N-vinylcaprolactam (VCL) and 2-(methacryloyloxy) ethyldimethyl-(3-sulfopropyl) ammonium hydroxide (DMAPS) via aqueous precipitation polymerization. The prepared nanogels own ultra-high colloidal stability and non-specific protein adsorption resistance as a result of the incorporation of zwitterionic groups. Meanwhile, they exhibit sensitive temperature-induced swelling/collapse transition in aqueous solution and excellent redox-degradability ascribed to the presence of disulfide bonds. The nanogels loaded with anticancer drug doxorubicin (DOX) exhibit low leakage of DOX under physiological conditions (merely 23.8 % within 24 h), whereas striking release amount of DOX under reducing conditions combined with elevated temperature (93.4 % within 24 h). The measurement of cell viability showed that the cytotoxicity of blank nanogels to tumor cells (HeLa cells) was negligible, while the nanogels loaded with DOX had a prominent inhibitory impact on tumor cells.

Nanostructures, Thermoresponsiveness, and Assembly Mechanism of Hydrogel Microspheres during Aqueous Free-Radical Precipitation Polymerization.

Although techniques to produce uniformly sized hydrogel microspheres (microgels) by aqueous free-radical precipitation polymerization are well established, the details of the polymerization process remain mysterious. In the present study, the structural evolution and thermoresponsiveness of the developing microgels during the polymerization were evaluated by temperature-controlled high-speed atomic force microscopy. This analysis clarified that the swelling properties of the precursor microgels formed in the early stages of the polymerization are quite low due to the high incorporation of cross-linkers and that non-thermoresponsive deca-nanosized spherical domains are already present in the precursor microgels. Furthermore, we succeeded in tracking the formation of nuclei and their growth process, which has never been fully understood, in aqueous solution by real-time observations. These findings will help us to design functional microgels with the desired nanostructures via precipitation polymerization.

Thermal Analysis and Crystal Structure of Poly(Acrylonitrile-Co-Itaconic Acid) Copolymers Synthesized in Water.

The composition and structure of polyacrylonitrile (PAN) precursors play an important role during thermal stabilization, which influences the properties of the resulting carbon fibers. In this paper, PAN homopolymer and PAN-itaconic (IA) copolymers with different IA contents were synthesized by aqueous phase precipitation polymerization. The effects of IA content on the structure and thermal properties were studied using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The morphology of PAN polymers showed that the average size of the PAN particles increased with the increase of IA content in the feed. The content of the IA comonomer on the copolymers was quantitatively characterized by the relative absorbance intensity (A1735/A2243) in FTIR spectrum. With the increase of IA content in the feed, PAN-IA copolymers exhibited lower degree of crystallinity and crystal size than the control PAN homopolymer. The results from DSC curves indicated that PAN-IA1.0 copolymers had lower initial exothermic temperature (192.4 °C) and velocity of evolving heat (6.33 J g−1 °C−1) in comparison with PAN homopolymer (Ti = 238.1 °C and ΔH/ΔT = 34.6 J g−1 °C−1) in an air atmosphere. TGA results suggested that PAN-IA1.0 copolymers had higher thermal stability than PAN homopolymer, which can form a ladder structure easier during thermal processing. Therefore, PAN-IA1.0 copolymers would be a suitable candidate for preparing high performance PAN based carbon fibers.

Facile modification of protein-imprinted polydopamine coatings over nanoparticles with enhanced binding selectivity

Mussel-inspired dopamine (DA) self-polymerization over a variety of substrates has become a simple but versatile approach for synthesis of surface protein-imprinted materials. However, relatively high nonspecific binding to the imprinted polydopamine (PDA) coatings has long been an open problem because of their multifunctionalities. We herein propose a facile strategy for reduction of the nonspecific adsorption by covering the imprinted PDA coatings with slightly crosslinked nonlinear poly(ethylene glycol) (PEG) layers via aqueous precipitation polymerization before template removal. Vinyl groups are introduced onto the PDA coatings via Cu2+ mediated metal coordination for facilitating surface polymerization. The Cu2+ and embedded template are removed after polymerization. For proof of hypothesis, the protein imprinted PDA coatings were formed with SiO2 nanoparticles as representative nano-supports and lysozyme as a model protein template. Protein binding tests show that the grafted PEG layers with an optimized feed crosslinking degree can significantly enhance both recognition selectivity and specific binding capacity to the imprinted nanoparticles, typically with the imprinting factor increasing from 2.6 to 6.4. Also, the PEG layers can remarkably improve the stability of the PDA coatings in the acidic template removal solution. The presented strategy represents the first example for PEGylation of protein-imprinted PDA coatings, and may be extended for surface imprinting of other bio/organic molecules over other substrate materials.

Controlled synthesis of PEGylated surface protein-imprinted nanoparticles.

High recognition selectivity has been the main object in developing protein-imprinted materials. Here, we demonstrate a novel strategy for the controlled synthesis of PEGylated surface protein-imprinted nanoparticles with reduced nonspecific binding, which is based on sequential two steps of surface-initiated reversible addition-fragmentation chain transfer aqueous precipitation polymerization (SI-RAFT APP). Click chemistry was employed to construct hydrophilic nanocores with both high-density RAFT chain transfer agents and template-capturing groups. Through the first-step SI-RAFT APP, protein-imprinted nanoshells were formed over the nanocores using lysozyme as a model template. By the second-step SI-RAFT APP, nonlinear PEG chains were grafted from the core-shell imprinted nanoparticles before the removal of the template. Both the thickness of the imprinted nanoshells and the length of the grafted chains could be readily controlled by the polymerization time. Thus the obtained PEGylated core-shell particles exhibited greatly improved template binding selectivity compared with the non-PEGylated controls, typically with the imprinting factor increasing from 2.1 to 9.1. Meanwhile, the PEGylation process did not impair but significantly enhance the protein binding capacity. The generality of the established approach was preliminarily proved by imprinting another template protein, bovine hemoglobin. This work represents the first example for the controlled synthesis and post-imprinting functionalization of surface protein-imprinted nanoparticles via SI-RAFT polymerization.

Molecular imprinting on PtPd nanoflowers for selective recognition and determination of hydrogen peroxide and glucose.

PtPd nanoflowers (PtPd NFs) exhibit intrinsic peroxidase-like activity as nanozymes, but the nanozymes lack substrate specificity and have low catalytic activity. Herein, a molecularly imprinted nanogel on PtPd NFs was prepared by using 3,3′,5,5′-tetramethylbenzidine (TMB) as the template through the aqueous precipitation polymerization method. After the TMB was washed out, many substrate binding pockets were retained in the PtPd NFs. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and powder X-ray diffraction (XRD) were employed to characterize the molecularly imprinted polymer (MIP) PtPd nanoflowers (T-MIP-PtPd NFs). The obtained T-MIP-PtPd NFs exhibited enhanced catalytic activity and specific recognition for TMB. Compared with PtPd NFs, T-MIP-PtPd NFs showed a linear range from 0.01–5000 μM and a detection limit of 0.005 μM toward the detection of H2O2. Glucose can also be sensitively detected through cascade reaction by the T-MIP-PtPd NFs and glucose oxidase. Therefore, molecular imprinting on nanozymes technology shows promising application in biocatalysis and sensing fields.

High-Speed AFM Reveals the Detailed Mechanism of Dynamic Protein Adsorption Onto Individual Hydrogel Microspheres

Hydrogel microspheres, i.e., microgels have both colloidal and hydrogel properties, which are composed of cross-linked hydrophilic polymer network. Due to the colloidal size property and biocompatibility, microgels are promising for advanced bio-nanomaterials such as protein drug delivery vehicles [1]. In order to establish the design concept of such protein carrier, understanding the dynamic interaction between the protein and microgels is essential. Up to now, the dynamic interaction between protein and microgels is well characterize by means of scattering, spectroscopy, and sensor [2]. However, to the best of our knowledge, there are no study that direct visualization during protein adsorption to individual microgels at nanoscale in real-time. Against this background, we visualized individual microgels during protein adsorption onto the microgels at nanoscale in real-time for the first time [3]. This approach, which enabled us to monitor the moment of protein adsorption to individual microgels, was realized by high-speed atomic force microscopy (HS-AFM) [4]. This method allows the direct visualization of the dynamics of biological molecules in action, without significantly disturbing the physiological function of the molecules [5]. We have already monitored the dynamic adsorption behavior of microgels onto solid/liquid interface [6]. The microgels were synthesized through aqueous free-radical precipitation polymerization of N-isopropyl acrylamide, the cross-linker N,N'-methylenebis (acrylamide), and acrylic acid with different content. In this presentation, the effect of protein interaction on the microgels’ dynamics will be discussed. Partially reproduced with permission from [6] Copyright (2017) John Wiley and Sons.

Real-Time Volume Changes in Individual Hydrogel Microspheres Observed By High-Speed AFM

Many thermo-responsive polymers show a lower critical solution temperature (LCST), and thus they display a coil-globule transition across the LCST by changing temperature. Hydrogel microspheres (microgels) composed of thermo-responsive polymer are taken over the property from the polymer, as a result, they show a volume phase transition temperature around the LCST. Owing to their rapid temperature-responsiveness, microgels are expected the various application such as sensors and separation technology [1]. Thermo-responsive properties of the microgels have been mainly evaluating by light scattering so far because typical size range of the microgels are tens nanometer to sub-micron order, which can not be clearly observed by optical microscopy. Against this background, the real-time volume transition of individual microgels during heating was visualized for the first time using high-speed atomic force microscopy (HS-AFM) [2]. This method allows the direct visualization of the structural dynamics of biological molecules in action, without significantly disturbing the physiological function of the molecules [3-4], and allows the monitoring dynamic adsorption behavior of microgels onto solid substrate in aqueous solution [5]. The microgels were synthesized from N-isopropyl acrylamide and cross-linker N,N'-methylenebis(acrylamide) with different content by aqueous free-radical precipitation polymerization. In the present study, we will discuss the real-time changes in morphology of the microgels. Partially reproduced with permission from [5] Copyright (2017) John Wiley and Sons.

Modelling the kinetics and structural property evolution of a versatile reaction: aqueous HCN polymerization.

The kinetics of the reaction of the synthesis of HCN polymers in aqueous medium at high temperatures have been analysed to ascertain a suitable model for this material, for which it was recently demonstrated that prebiotic chemistry may now be adapted in the development of a new generation of high performance coatings and adhesives with biomedical applications. These experimental conditions were chosen for the simplicity of the reagents, being particularly convenient in regard to potential industrial scale-up of coating technology, where these polymers have revealed an interesting field of application. The kinetics of the precipitation polymerization of HCN in water were studied under isothermal conditions at four different temperatures between 75 °C and 90 °C throughout gravimetric measurements. The use of the Kamal-Sourour autocatalytic kinetic model was proposed, properly describing the overall formation process of this insoluble HCN polymer. All of the kinetic parameters, including reaction orders, kinetic constants and activation energy, were determined for the cross-linking polymerization reaction under study, and a relevant autocatalysis effect was observed. An isoconversion method was also used to analyse the variation of the global activation energy with conversion; and characterization by means of elemental analysis, Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM) was carried out. This study demonstrates the autocatalytic, robust and straightforward character of this heterogeneous aqueous HCN polymerization, and to the best of our knowledge, this report describes the first time that a systematic and extended kinetic analysis has been conducted to obtain a more comprehensive and deeper understanding of this complex reaction, which is of great interest to the origin of life and, currently, to materials science.

The deformation of hydrogel microspheres at the air/water interface.

The deformation of soft hydrogel microspheres (microgels) adsorbed at the air/water interface was investigated for the first time using large poly(N-isopropyl acrylamide)-based microgels synthesized by a modified aqueous precipitation polymerization method. The deformation of the micron-sized soft microspheres could be visualized clearly and analyzed quantitatively at the air/water interface.

Synthesis of thermo-responsive bovine hemoglobin imprinted nanoparticles by combining ionic liquid immobilization with aqueous precipitation polymerization.

Surface molecular imprinting over functionalized nanoparticles has proved to be an effective approach for construction of artificial nanomaterials for protein recognition. Herein, we report a strategy for synthesis of core-shell protein-imprinted nanoparticles by the functionalization of nano-cores with ionic liquids followed by aqueous precipitation polymerization to build thermo-responsive imprinted polymer nano-shells. The immobilized ionic liquids can form multiple interactions with the protein template. The polymerization process can produce thermo-reversible physical crosslinks, which are advantageous to enhancing imprinting and facilitating template removal. With bovine hemoglobin as a model template, the imprinted nanoparticles showed temperature-sensitivity in both dispersion behaviors and rebinding capacities. Compared with the ionic-liquid-modified core nanoparticles, the imprinted particles exhibited greatly increased selectivity and two orders of magnitude higher binding affinity for the template protein. The imprinted nanoparticles achieved relatively high imprinting factor up to 5.0 and specific rebinding capacity of 67.7mg/g, respectively. These nanoparticles also demonstrated rapid rebinding kinetics and good reproducibility after five cycles of adsorption-regeneration. Therefore, the presented approach may be viable for the fabrication of high-performance protein-imprinted nanoparticles with temperature sensitivity.

Nanohydrogel with N,N′-bis(acryloyl)cystine crosslinker for high drug loading

Substantially improved hydrogel particles based on poly(N-isopropylacrylamide) (pNIPA) have been obtained. First, as a result of replacing commercially available N,N′-bis(acryloyl)cystamine (BAC), the crosslinker, with acryloyl derivative of cystine containing a carboxylic group (BISS), the hydrogel particles acquired improved stability vs. ionic strength and allowed further chemical modification of the chains, including the attachment of drug molecules. Next, a redox-initiated aqueous precipitation polymerization via the semi-batch method was used. This led to substantially increased BISS content and diminished size of the nanoparticles that made them suitable to an endocytic process. In addition, the obtained nanogels revealed high loading capacity of anticancer drug vs. dry gel (circa 16%) and they exhibited much better stability and enhanced drug release under the typical conditions existing in cancer cells. Size of obtained nanogels was investigated by dynamic light scattering (DLS). It appeared that nanoparticle size was in the range from ca. 40 to 200nm. In 0.01M solution of glutathione (GSH) the -S-S- bonds were reduced and the nanogel particles were degraded. This could be seen in obtained SEM and TEM micrographs. The cytotoxicity investigation against the HeLa cells showed that DOX loaded nanogels were more cytotoxic (IC50=0.51μM) than free DOX (IC50=0.83μM), while unloaded nanogels did not inhibit proliferation of the cells. It was also found that the nanogels loaded with DOX reached a high intracellular concentration in HeLa cells just after 2h while free DOX needed 6h for that.

Preparation and adsorption properties of molecularly imprinted polymer via RAFT precipitation polymerization for selective removal of aristolochic acid I

The molecularly imprinted polymers (MIP) were prepared via aqueous RAFT precipitation polymerization, with aristolochic acid I (AAI) as the template molecule, AA as the functional monomer, EGDMA as the cross-linker, AIBN as the chain initiator, CTP as the chain transfer agent and 80% (g/g) DMF-aqueous solution as the porogen. The differential UV–vis spectra revealed that a cooperative hydrogen-bonding complex between AAI and AA might be formed at the molar ratio of 1:3 in prepolymerized system. The synthesized MIPs were characterized by FTIR spectra, solid UV–visible absorption spectra, nitrogen adsorption-desorption isotherms and scanning electron microscope, which proved that the MIPs and NIPs have the similar chemical structures and the adding of AAI could affect the size and morphology of the microspheres. UV–visible absorption spectra and High-performance liquid chromatography (HPLC) was used to investigate the adsorption and recognition properties of the MIPs. The Scatchard isotherm model described that the binding sites independently acted. The Langmuir isotherm model suggested an excellent imprinting effect owing to the presence of a large number of specific binding sites on the MIP. The Freundlich model indicated that the AAI could be readily absorbed by MIP. Selective absorption of the template molecule was demonstrated in presence of its analogous compounds, benzoic acid and nitrobenzene. The recycling experiments implied that the MIP could be reused to further selective recognition and separation to AAI for six times at least. MIP was developed for removal of AAI from the Aristolochia manshuriensis extraction. The results indicated that 25mg of MIP could remove the AAI below the HPLC detection limits (6.47ngmL-1) from 5.0mL of the extraction (CAAI=0.0018mgmL-1) with the recovery of AAI to 91.50% (n=3, SD=4.24%). Therefore, it is clearly revealed that the MIP can be a useful tool to remove toxic compounds from natural products.

Fabrication of biocompatible and stimuli-responsive hybrid microgels with magnetic properties via aqueous precipitation polymerization

This article reports the fabrication of poly(N-vinylcaprolactam-co-itaconic acid)- (poly(NVCL-co-IA))-based microgels containing magnetic nanoparticles. Preformed iron oxide nanoparticles that were functionalized with oleic acid and the reactive surfactant dodecan-1-ene-1-sodium sulfonate were used for such a purpose. NVCL and IA were polymerized in situ from the functionalized iron oxide nanoparticle surfaces. The process resulted in hybrid microgels with size between 166.9 and 193.3nm. The polydispersity index was low, which indicated that the microgels' magnetic dispersion is stable and homogeneous. The hydrid poly(NVCL-co-IA)-based microgels showed both temperature- and pH-sensitive behavior. The addition of iron oxide to the microgels was confirmed qualitatively by FTIR, X-ray diffraction and magnetization. The transmission electron microscopy (TEM) images confirmed the spherical morphology of the hybrid microgel which had a core that consisted of magnetic nanoparticles surrounded by a polymeric shell. Finally, the biocompatibility of (poly(NVCL-co-IA)) microgel containing magnetic nanoparticles was confirmed in vitro. All together, these results indicate the feasibility of the hybrid microgel to be used as a new drug delivery system.

Thermo- and salt-responsive poly(NIPAm-co-AAc-Brij-58) microgels: adjustable size, stability under salt stimulus, and rapid protein adsorption/desorption

Based on N-isopropylacrylamide (NIPAm) and modified copolymer of liquid crystal surfactant polyoxyethylene 20 cetyl ether (AAc-Brij-58), a series of “smart” poly(NIPAm-co-AAc-Brij-58) (ACM) microgels with controllable particle size and adjustable salt stability have been successfully fabricated by aqueous precipitation polymerization. The stability under the stimulus of salt and protein adsorption/desorption behavior of ACM microgels were explored. It can be found that when the mass percentage of AAc-Brij-58/NIPAm is 1 wt.%, the ACM01 microgel film presents the lowest contact angel (ca. 35.9°) and the highest hydrodynamic diameters (D H) value (ca. 1100 nm) with the increase of volume phase transition temperature (VPTT). In terms of transmittance change versus different concentrations of NaCl solution and transmittance versus temperature under certain salt concentrations, the responsibility of ACM microgel under ionic strength is investigated sufficiently. The adsorption/desorption behavior of ACM microgels to Bovine Serum Albumin (BSA) is also revealed. The results show that the maximum adsorption amount of AMC01 to BSA reaches 982.7 ± 26 mg/g at 25 °C, much higher than that of ACM0 (714.7 ± 36 mg/g) and ACM02 microgels (402 ± 20 mg/g).

Fabrication of Surface Protein-Imprinted Nanoparticles Using a Metal Chelating Monomer via Aqueous Precipitation Polymerization.

Molecular imprinting is a promising way for constructing artificial protein recognition materials, but it has been challenged by difficulties such as restricted biomacromolecule transfer in the cross-linked polymer networks, and reduced template-monomer interactions that are due to the required aqueous media. Herein, we propose a strategy for imprinting of histidine (His)-exposed proteins by combining previous approaches such as surface imprinting over nanostructures, utilization of metal coordination interactions, and adoption of aqueous precipitation polymerization capable of forming reversible physical crosslinks. With lysozyme as a model template bearing His residues, imprinted polymer nanoshells were grafted over vinyl-modified nanoparticles by aqueous precipitation copolymerization of a Cu(2+) chelating monomer with a temperature-responsive monomer carried out at 37 °C, above the volume phase-transition temperature (VPTT) of the final copolymer. The imprinted nanoshells showed significant temperature sensitivity and the template removal could be facilitated by swelling of the imprinted layers at 4 °C, below the VPTT. The resultant core-shell imprinted nanoparticles exhibited strikingly high rebinding selectivity against a variety of nontemplate proteins. An imprinting factor up to 22.7 was achieved, which is among the best values reported for protein imprinting, and a rather high specific binding capacity of 67.3 mg/g was obtained. Moreover, this approach was successfully extended to preliminary imprinting of hemoglobin, another protein with accessible His. Therefore, it may be a versatile method for fabrication of high-performance surface-imprinted nanoparticles toward His-exposed proteins.

Synthesis of surface protein-imprinted nanoparticles endowed with reversible physical cross-links.

Researches on protein molecularly imprinted polymers have been challenged by the difficulties in facilitating biomacromolecular transfer, in particular upon the template removal step, and enhancing their recognition performance. Addressing these issues, herein we report synthesis of core–shell structured surface protein-imprinted nanoparticles with reversible physical cross-links formed in the imprinted nanoshells. The imprinted layers over nanoparticle supports are fabricated via aqueous precipitation polymerization (PP) of di(ethylene glycol) methyl ether methacrylate (MEO2MA), a thermo-responsive monomer bearing no strong H-bond donor, and other functional and cross-linking monomers. During polymerization, physical cross-links together with chemical cross-links are in site produced within the imprinted shells based on hydrophobic association among the PMEO2MA, favoring formation of high-quality imprints. While cooled appropriately below the polymerization temperature, these physical cross-links can be dissociated rapidly, thus facilitating removal of the embedded template. For proof of this concept, lysozyme-imprinted nanoparticles were synthesized at 37 °C over the nanoparticles functionalized with carboxylic and vinyl groups. The template removal from the imprinted nanoparticles was readily achieved by washing with a dilute acidic detergent solution at 4 °C. As-prepared imprinted nanoparticles showed greatly higher imprinting factor and specific rebinding than obtained with the same recipe but by solution polymerization (SP). Moreover, such imprinted nanomaterials exhibited satisfactory rebinding selectivity, kinetics and reusability.